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Díez-Solinska A, De Miguel Z, Azkona G, Vegas O. Behavioral coping with chronic defeat stress in mice: A systematic review of current protocols. Neurobiol Stress 2024; 33:100689. [PMID: 39628708 PMCID: PMC11612788 DOI: 10.1016/j.ynstr.2024.100689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 10/18/2024] [Accepted: 11/06/2024] [Indexed: 12/06/2024] Open
Abstract
Social stress is the most significant source of chronic stress in humans and is commonly associated with health impairment. Individual differences in the behavioral coping responses to stress have been proposed to mediate the negative effects of stress on physical, behavioral and mental health. Animal models, particularly mice, offer valuable insights into the physiological and neurobiological correlates of behavioral coping strategies in response to chronic social stress. Here we aim to identify differences and similarities among stress protocols in mice, with particular attention to how neuroendocrine and/or behavioral responses vary according to different coping strategies, while highlighting the need for standardized approaches in future research. A systematic review was undertaken following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA statement). A total of 213 references were identified by electronic search, and after the screening, 18 articles were found to meet all the established criteria. We analyzed differences in the stress protocol, the characterization and classification of coping strategies and the physiological and behavioral differences according to coping. The results show that differences in behavioural expression under chronic social stress (coping) may also be associated with physiological differences and differential susceptibility to disease. However, this review also underlines the importance of a cautious interpretation of the results obtained. The lack of consistency in the nomenclature and procedures associated with the study of coping strategies for social stress, as well as the absence of a uniform classification, highlight the importance of using a common language when approaching the study of coping strategies. Thereby, this review encourages the development of a more defined method and criteria for assessing coping strategies, based on both behavioral and biological indicators.
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Affiliation(s)
- Alina Díez-Solinska
- Department of Basic Psychological Processes and Their Development, University of the Basque Country UPV/EHU, 20018, Donostia-San Sebastian, Spain
| | - Zurine De Miguel
- Department of Psychology, California State University, Monterey Bay, CA, USA
- Department of Health Sciences, Public University of Navarre UPNA, 31006, Pamplona, Spain
| | - Garikoitz Azkona
- Department of Basic Psychological Processes and Their Development, University of the Basque Country UPV/EHU, 20018, Donostia-San Sebastian, Spain
| | - Oscar Vegas
- Department of Basic Psychological Processes and Their Development, University of the Basque Country UPV/EHU, 20018, Donostia-San Sebastian, Spain
- Biogipuzkoa Health Research Institute, 20014, Donostia-San Sebastian, Spain
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Liao WC, Lo SW, Wu CL, Juang SE, Chang HC, Gau SY, Li CP. Herpes Zoster Risk After Total Knee Replacement: a multicenter, propensity-score-matched cohort study in the United States. Int J Med Sci 2024; 21:2244-2251. [PMID: 39310252 PMCID: PMC11413905 DOI: 10.7150/ijms.97654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 08/09/2024] [Indexed: 09/25/2024] Open
Abstract
Background: Total knee replacement (TKR) is a common surgical procedure for osteoarthritis (OA) patients. TKR may increase susceptibility to herpes zoster (HZ) by inducing immunosuppression, surgical stress, and nerve injury. However, limited data exist on the relationship between TKR and HZ. This study examined the risk of HZ over time among OA patients who underwent TKR and those who did not, using a large population-based cohort. Method: Utilizing the TriNetX research network, people with OA and underwent TKR were recruited as case group. After 1:1 propensity score matching, OA patients who never experienced TKR were included as control group. Covariates, including demographics, comorbidities, and laboratory data, were balanced using propensity score matching. A 5-year follow-up assessed the hazard ratio of incident HZ and related complications. Results: Compared to the control group, a significantly elevated risk of HZ was observed in the TKR cohort across 5-year follow-up period, with the hazard ratio of 1.223 (95% CI: 1.089-1.373). Zoster without complications presented 1.173-fold risk in TKR patients while comparing with non-TKR controls. However, most other secondary outcomes related to HZ complications-such as encephalitis, neurological involvement, ocular disease, and disseminated zoster-did not show a significant increase in risk. The risk of HZ was statistically significant for females and older adults in the TKR cohort than in the control cohort. Conclusions: OA patients who underwent TKR had an increased risk of HZ compared to those who did not receive the procedure, especially females and older adults. These findings highlight the need for HZ monitoring/prevention protocols and further research on mitigating viral reactivation after major joint surgery.
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Affiliation(s)
- Wen-Chieh Liao
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Doctoral Program in Tissue Engineering and Regenerative Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Shao-Wei Lo
- Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Chih-Lung Wu
- Department of Orthopedic Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Sin-Ei Juang
- Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hui-Chin Chang
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Evidence-based Medicine Center, Chung Shan Medical University Hospital, Taichung, Taiwan
- Library, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Shuo-Yan Gau
- Department and Graduate Institute of Business Administration, National Taiwan University, Taipei, Taiwan
- Department of Pharmacology, Chung Shan Medical University, Taichung, Taiwan
- Orthopedics Department, Chi-Mei Medical Center, Tainan, Taiwan
| | - Chen-Pi Li
- Department of Nursing & Tungs' Taichung MetroHarbor Hospital, Taiwan
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Ghareeb AFA, Foutz JC, Schneiders GH, Richter JN, Milfort MC, Fuller AL, Rekaya R, Aggrey SE. Host transcriptome response to heat stress and Eimeria maxima infection in meat-type chickens. PLoS One 2024; 19:e0296350. [PMID: 38394169 PMCID: PMC10889870 DOI: 10.1371/journal.pone.0296350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Accepted: 12/05/2023] [Indexed: 02/25/2024] Open
Abstract
Eimeria (E.) maxima parasite infects chickens' midgut disrupting the jejunal and ileal mucosa causing high morbidity and mortality. Heat stress (HS) is a seasonal stressor that impacts biological functions leading to poor performance. This study elucidates how HS, E. maxima infection, and their combination affect the ileum transcriptome. Two-hundred and forty 2-week-old males Ross708 chickens were randomly allocated into four treatment groups: thermoneutral-control (TNc), thermoneutral-infected (TNi), heat-stress control (HSc), and heat stress-infected (HSi), with 6 replicates each of 10 birds. Infected groups received 200x103 sporulated E. maxima oocysts/bird, and heat-treated groups were raised at 35°C. At 6-day post-treatment, ileums of five randomly selected chickens per group were sampled, RNA was extracted and sequenced. A total of 413, 3377, 1908, and 2304 DEGs were identified when applying the comparisons: TNc vs HSc, TNc vs TNi, HSi vs HSc, and TNi vs HSi, respectively, at cutoff ≥1.2-fold change (FDR: q<0.05). HSc vs TNc showed upregulation of lipid metabolic pathways and degradation/metabolism of multiple amino acids; and downregulation of most immune-related and protein synthesis pathways. TNc vs TNi displayed upregulation of most of immune-associated pathways and eukaryotic mRNA maturation pathways; and downregulation of fatty acid metabolism and multiple amino acid metabolism pathways including tryptophan. Comparing HSi versus HSc and TNi revealed that combining the two stressors restored the expression of some cellular functions, e.g., oxidative phosphorylation and protein synthesis; and downregulate immune response pathways associated with E. maxima infection. During E. maxima infection under HS the calcium signaling pathway was downregulated, including genes responsible for increasing the cytoplasmic calcium concentration; and tryptophan metabolism was upregulated, including genes that contribute to catabolizing tryptophan through serotonin and indole pathways; which might result in reducing the cytoplasmic pool of nutrients and calcium available for the parasite to scavenge and consequently might affect the parasite's reproductive ability.
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Affiliation(s)
- Ahmed F. A. Ghareeb
- NutriGenomics Laboratory, Department of Poultry Science, University of Georgia, Athens, Georgia, United States of America
| | - James C. Foutz
- NutriGenomics Laboratory, Department of Poultry Science, University of Georgia, Athens, Georgia, United States of America
| | - Gustavo H. Schneiders
- NutriGenomics Laboratory, Department of Poultry Science, University of Georgia, Athens, Georgia, United States of America
| | - Jennifer N. Richter
- NutriGenomics Laboratory, Department of Poultry Science, University of Georgia, Athens, Georgia, United States of America
| | - Marie C. Milfort
- NutriGenomics Laboratory, Department of Poultry Science, University of Georgia, Athens, Georgia, United States of America
| | - Alberta L. Fuller
- NutriGenomics Laboratory, Department of Poultry Science, University of Georgia, Athens, Georgia, United States of America
| | - Romdhane Rekaya
- Department of Animal and Dairy Science, University of Georgia, Athens, Georgia, United States of America
| | - Samuel E. Aggrey
- NutriGenomics Laboratory, Department of Poultry Science, University of Georgia, Athens, Georgia, United States of America
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Gilstrap SR, Hobson JM, Owens MA, White DM, Sammy MJ, Ballinger S, Sorge RE, Goodin BR. Mitochondrial reactivity following acute exposure to experimental pain testing in people with HIV and chronic pain. Mol Pain 2023; 19:17448069231195975. [PMID: 37542365 PMCID: PMC10467217 DOI: 10.1177/17448069231195975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 07/06/2023] [Accepted: 08/03/2023] [Indexed: 08/06/2023] Open
Abstract
Background: Physical stressors can cause a physiological response that can contribute to an increase in mitochondrial dysfunction and Mitochondrial DNA damage (mtDNA damage). People living with HIV (PWH) are more likely to suffer from chronic pain and may be more susceptible to mitochondrial dysfunction following exposure to a stressor. We used Quantitative Sensory Testing (QST) as an acute painful stressor in order to investigate whether PWH with/without chronic pain show differential mitochondrial physiological responses. Methods: The current study included PWH with (n = 26), and without (n = 29), chronic pain. Participants completed a single session that lasted approximately 180 min, including QST. Blood was taken prior to and following the QST battery for assays measuring mtDNA damage, mtDNA copy number, and mtDNA damage-associated molecular pattern (DAMP) levels (i.e., ND1 and ND6). Results: We examined differences between those with and without pain on various indicators of mitochondrial reactivity following exposure to QST. However, only ND6 and mtDNA damage were shown to be statistically significant between pain groups. Conclusion: PWH with chronic pain showed greater mitochondrial reactivity to laboratory stressors. Consequently, PWH and chronic pain may be more susceptible to conditions in which mitochondrial damage/dysfunction play a central role, such as cognitive decline.
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Affiliation(s)
- Shannon R Gilstrap
- Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Joanna M Hobson
- Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Michael A Owens
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA
| | - Dyan M White
- Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Melissa J Sammy
- Bio-Analytical Research Biology (BARB) Core, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Scott Ballinger
- Bio-Analytical Research Biology (BARB) Core, University of Alabama at Birmingham, Birmingham, AL, USA
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Robert E Sorge
- Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Burel R Goodin
- Department of Anesthesiology, Washington University, St Louis, MO, USA
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Guo Y, Schon L, Paudel S, Feltham T, Manandhar L, Zhang Z. Increased synovial expression of calcitonin gene-related peptide and its potential roles in Charcot Neuroarthropathy. Exp Mol Pathol 2022; 128:104835. [PMID: 36195300 DOI: 10.1016/j.yexmp.2022.104835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 09/19/2022] [Accepted: 09/28/2022] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Joint destruction in Charcot neuroarthropathy (CNA) is accompanied with abundant hyperplastic synovium. This study aimed to characterize the expression patterns of a group of neuropeptides in the CNA synovium. METHODS Synovial specimens were collected during surgery from the CNA (n = 6) and non-CNA joints (n = 14). Tissue samples were processed for protein extraction and western blot for vasoactive intestinal peptide (VIP), galanin, and calcitonin gene-related peptide (CGRP). Immunohistochemistry was performed to localize CGRP in the CNA synovium. Additionally, CGRP was applied to fibroblast-like synoviocytes (FLS) isolated from CNA synovium for its effects on cell proliferation and collagenolysis in vitro. RESULTS Western blot detected light bands of VIP in the CNA samples but abundant galanin in both CNA and non-CNA samples. Most of the CNA samples (5/6) increased expression of CGRP, with an average band density about 2 times that in the non-CNA group (p < .05). Immunohistochemistry of CGRP demonstrated intense staining in the intimal layer of the CNA synovium. In tissue culture, adding CGRP (10 nM) in the medium promoted FLS proliferation. In combination with TNF-α, CGRP enhanced FLS-mediated collagenolysis in vitro. CONCLUSION This study revealed an increased expression of CGRP in the CNA synovium and demonstrated that CGRP regulates FLS proliferation and collagenolytic activity, suggesting CGRP may contribute to the bone and cartilage destruction in CNA.
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Affiliation(s)
- Yi Guo
- Department of Orthopaedic Surgery, Montefiore Medical Center, Bronx, NY, USA
| | - Lew Schon
- Institute for Foot and Ankle Reconstruction, Mercy Medical Center, Baltimore, MD, USA; Center for Orthopaedic Innovation, Mercy Medical Center, Baltimore, MD, USA
| | - Sharada Paudel
- Frederick National Laboratory for Cancer Research, Frederick, MD, USA
| | - Tyler Feltham
- Philadelphia College of Osteopathic Medicine-GA, Suwanee, GA, USA
| | | | - Zijun Zhang
- Center for Orthopaedic Innovation, Mercy Medical Center, Baltimore, MD, USA.
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Hamed SA, Elwasify M, Abdelhafez M, Fawzy M. Peripartum depression and its predictors: A longitudinal observational hospital-based study. World J Psychiatry 2022; 12:1061-1075. [PMID: 36158302 PMCID: PMC9476840 DOI: 10.5498/wjp.v12.i8.1061] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 01/08/2022] [Accepted: 07/18/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Depression is a common problem in women in childbearing years due to burdens of motherhood and building a family. Few studies estimate the prevalence of antepartum depression compared to those in the postpartum period. AIM To estimate the prevalence and the severities of peripartum depression and major depressive disorder and their predictors. METHODS This is a longitudinal observation study. It included 200 women scoring ≥ 13 with the Edinburgh Postpartum Depression Scale, indicating presence of symptoms of depression. They had a gestational age of ≥ 6 wk and did follow-ups until the 10th week to 12th weeks postpartum. Information of women's reactions to life circumstances and stressors during the current pregnancy were gathered from answers to questions of the designed unstructured clinical questionnaire. Severities of depression, anxiety, and parenting stress were determined by the Beck Depre-ssion Inventory, State-Trait Anxiety Inventory for Adults, and Parenting Stress Index-Short Form, respectively. Psychiatric interviewing was done to confirm the diagnosis of major depression. Measuring the levels of triiodothronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) was done in both antepartum and postpartum periods. RESULTS Out of 968 (mean age = 27.35 ± 6.42 years), 20.66% (n = 200) of the patients had clinically significant symptoms of depression and 7.44% had major depression. Previous premenstrual dysphoria, post-abortive depression, and depression unrelated to pregnancy and were reported in 43%, 8%, and 4.5% of the patients, respectively. Psychosocial stressors were reported in 15.5% of the patients. Antepartum anxiety and parenting stress were reported in 90.5% and 65% of the patients, respectively. Postpartum T3, T4, and TSH levels did not significantly differ from reference values. Regression analysis showed that anxiety trait was a predictor for antepartum (standardized regression coefficients = 0.514, t = 8.507, P = 0.001) and postpartum (standardized regression coefficients = 0.573, t = 0.040, P = 0.041) depression. Antepartum depression (standardized regression coefficients = -0.086, t = -2.750, P = 0.007), and parenting stress (standardized regression coefficients = 0.080, t = 14.34, P = 0.0001) were also predictors for postpartum depression. CONCLUSION Results showed that 20.66% of the patients had clinically significant symptoms of depression and 7.44% had major depression. Anxiety was a predictor for antepartum and postpartum depression. Antepartum depression and parenting stress were also predictors for postpartum depression.
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Affiliation(s)
- Sherifa Ahmed Hamed
- Department of Neurology and Psychiatry, Assiut University Hospital, Assiut 71516, Egypt
| | - Mohamed Elwasify
- Department of Psychiatry, Mansoura University, Mansoura 11001, Egypt
| | - Mohamed Abdelhafez
- Department of Obstetrics and Gynecology, Mansoura University, Mansoura 11001, Egypt
| | - Mohamed Fawzy
- Department of Neurology and Psychiatry, Assiut University Hospital, Assiut 71516, Egypt
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Saier MH, Baird SM, Reddy BL, Kopkowski PW. Eating Animal Products, a Common Cause of Human Diseases. Microb Physiol 2022; 32:146-157. [PMID: 35952632 PMCID: PMC11330319 DOI: 10.1159/000526443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 07/08/2022] [Indexed: 08/19/2024]
Abstract
The human population is plagued by hundreds of infectious agents that cause diseases, and many of these agents can infect a range of wild and domesticated animals as well. In fact, a large proportion of current pathological conditions in humans is caused by our close association with nonhuman animals, some of which we keep as pets, but most of which we raise, prepare as food sources, and ingest. It is well established that most of these diseases are caused by a variety of infectious agents, the most important being bacteria, viruses, prions, and protozoans. In this article, we shall consider these agents and discuss their transmission from various animals and animal products to humans. It is noted that virtually none of these agents are obtained by eating plant-derived products unless the plants are grown and prepared with contaminated water. Consequently, we suggest that Homo sapiens could avoid a significant fraction of the diseases that plague us by shifting to a more vegetarian diet.
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Affiliation(s)
- Milton H Saier
- Department of Molecular Biology, University of California at San Diego, La Jolla, California, USA
| | - Stephen M Baird
- Department of Molecular Biology, University of California at San Diego, La Jolla, California, USA
| | - B Lakshmi Reddy
- Department of Molecular Biology, University of California at San Diego, La Jolla, California, USA
| | - Peter W Kopkowski
- Department of Molecular Biology, University of California at San Diego, La Jolla, California, USA,
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8
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Ahmed U, Graf JF, Daytz A, Yaipen O, Mughrabi I, Jayaprakash N, Cotero V, Morton C, Deutschman CS, Zanos S, Puleo C. Ultrasound Neuromodulation of the Spleen Has Time-Dependent Anti-Inflammatory Effect in a Pneumonia Model. Front Immunol 2022; 13:892086. [PMID: 35784337 PMCID: PMC9244783 DOI: 10.3389/fimmu.2022.892086] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 05/17/2022] [Indexed: 12/27/2022] Open
Abstract
Interfaces between the nervous and immune systems have been shown essential for the coordination and regulation of immune responses. Non-invasive ultrasound stimulation targeted to the spleen has recently been shown capable of activating one such interface, the splenic cholinergic anti-inflammatory pathway (CAP). Over the past decade, CAP and other neuroimmune pathways have been activated using implanted nerve stimulators and tested to prevent cytokine release and inflammation. However, CAP studies have typically been performed in models of severe, systemic (e.g., endotoxemia) or chronic inflammation (e.g., collagen-induced arthritis or DSS-induced colitis). Herein, we examined the effects of activation of the splenic CAP with ultrasound in a model of local bacterial infection by lung instillation of 105 CFU of Streptococcus pneumoniae. We demonstrate a time-dependent effect of CAP activation on the cytokine response assay during infection progression. CAP activation-induced cytokine suppression is absent at intermediate times post-infection (16 hours following inoculation), but present during the early (4 hours) and later phases (48 hours). These results indicate that cytokine inhibition associated with splenic CAP activation is not observed at all timepoints following bacterial infection and highlights the importance of further studying neuroimmune interfaces within the context of different immune system and inflammatory states.
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Affiliation(s)
- Umair Ahmed
- Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, United States
| | - John F. Graf
- General Electric Research, Niskayuna, NY, United States
| | - Anna Daytz
- Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, United States
| | - Omar Yaipen
- Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, United States
| | - Ibrahim Mughrabi
- Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, United States
| | - Naveen Jayaprakash
- Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, United States
| | | | | | - Clifford Scott Deutschman
- Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, United States
| | - Stavros Zanos
- Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, United States
| | - Chris Puleo
- General Electric Research, Niskayuna, NY, United States
- *Correspondence: Chris Puleo,
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9
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Carnevale D. Neuroimmune axis of cardiovascular control: mechanisms and therapeutic implications. Nat Rev Cardiol 2022; 19:379-394. [PMID: 35301456 DOI: 10.1038/s41569-022-00678-w] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/07/2022] [Indexed: 12/21/2022]
Abstract
Cardiovascular diseases (CVDs) make a substantial contribution to the global burden of disease. Prevention strategies have succeeded in reducing the effect of acute CVD events and deaths, but the long-term consequences of cardiovascular risk factors still represent the major cause of disability and chronic illness, suggesting that some pathophysiological mechanisms might not be adequately targeted by current therapies. Many of the underlying causes of CVD have now been recognized to have immune and inflammatory components. However, inflammation and immune activation were mostly regarded as a consequence of target-organ damage. Only more recent findings have indicated that immune dysregulation can be pathogenic for CVD, identifying a need for novel immunomodulatory therapeutic strategies. The nervous system, through an array of afferent and efferent arms of the autonomic nervous system, profoundly affects cardiovascular function. Interestingly, the autonomic nervous system also innervates immune organs, and neuroimmune interactions that are biologically relevant to CVD have been discovered, providing the foundation to target neural reflexes as an immunomodulatory therapeutic strategy. This Review summarizes how the neural regulation of immunity and inflammation participates in the onset and progression of CVD and explores promising opportunities for future therapeutic strategies.
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Affiliation(s)
- Daniela Carnevale
- Department of Molecular Medicine, Sapienza University, Rome, Italy. .,Research Unit of Neuro and Cardiovascular Pathophysiology, IRCCS Neuromed, Pozzilli, Italy.
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Madkour M, Salman FM, El-Wardany I, Abdel-Fattah SA, Alagawany M, Hashem NM, Abdelnour SA, El-Kholy MS, Dhama K. Mitigating the detrimental effects of heat stress in poultry through thermal conditioning and nutritional manipulation. J Therm Biol 2022; 103:103169. [PMID: 35027188 DOI: 10.1016/j.jtherbio.2021.103169] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 12/09/2021] [Accepted: 12/16/2021] [Indexed: 12/20/2022]
Abstract
The poultry industry faces several obstacles and challenges, including the changes in global temperature, increase in the per capita demand for meat and eggs, and the emergence and spread of various diseases. Among these, environmental challenges are one of the most severe hurdles impacting the growth and productivity of poultry. In particular, the increasing frequency and severity of heat waves over the past few years represent a major challenge, and this is expected to worsen in the coming decades. Chickens are highly susceptible to high ambient temperatures (thermal stress), which negatively affect their growth and productivity, leading to enormous economic losses. In the light of global warming, these losses are expected to increase in the near future. Specifically, the worsening of climate change and the rise in global temperatures have augmented the adverse effects of heat on poultry production worldwide. At present, the world population is approximately 7.9 billion, and it has been predicted to reach 9.3 billion by 2050 and approximately 11 billion by 2100, implying a great demand for protein supply; therefore, strategies to mitigate future poultry challenges must be urgently devised. To date, several mitigation measures have been adopted to minimize the negative effects of heat stress in poultry. Of these, thermal acclimation at the postnatal stage or throughout the embryonic stages has been explored as a promising approach; however, for large-scale application, this approach warrants further investigation to determine the suitable temperature and poultry age. Moreover, molecular mechanisms governing thermal conditioning are poorly understood. To this end, we sought to expand our knowledge of thermal conditioning in poultry, which may serve as a valuable reference to improve the thermotolerance of chickens via nutritional management and vitagene regulation. Vitagenes regulate the responses of poultry to diverse stresses. In recent years, nutritionists have paid close attention to bioactive compounds such as resveratrol, curcumin, and quercetin administered alone or in combination. These compounds activate vitagenes and other regulators of the antioxidant defense system, such as nuclear factor-erythroid 2-related factor 2. Overall, thermal conditioning may be an effective strategy to mitigate the negative effects of heat stress. In this context, the present review synthesizes information on the adverse impacts of thermal stress, elucidating the molecular mechanisms underlying thermal conditioning and its effects on the acquisition of tolerance to acute heat stress in later life. Finally, the role of some polyphenolic compounds, such as resveratrol, curcumin, and quercetin, in attenuating heat stress through the activation of the antioxidant defense system in poultry are discussed.
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Affiliation(s)
- Mahmoud Madkour
- Animal Production Department, National Research Centre, Dokki, 12622, Giza, Egypt.
| | - Fatma M Salman
- Animal Production Department, National Research Centre, Dokki, 12622, Giza, Egypt
| | - Ibrahim El-Wardany
- Poultry Production Department, Faculty of Agriculture, Ain Shams University, Shoubra El-Kheima, 11241, Cairo, Egypt
| | - Sayed A Abdel-Fattah
- Poultry Production Department, Faculty of Agriculture, Ain Shams University, Shoubra El-Kheima, 11241, Cairo, Egypt
| | - Mahmoud Alagawany
- Poultry Department, Faculty of Agriculture, Zagazig University, Zagazig, Egypt
| | - Nesrein M Hashem
- Department of Animal and Fish Production, Faculty of Agriculture (El-Shatby), Alexandria University, Alexandria, 21545, Egypt
| | - Sameh A Abdelnour
- Department of Animal Production, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt
| | - Mohamed S El-Kholy
- Poultry Department, Faculty of Agriculture, Zagazig University, Zagazig, Egypt
| | - Kuldeep Dhama
- Division of Pathology, Indian Veterinary Research Institute (IVRI), Izatnagar, Bareilly, 243 122, Uttar Pradesh, India
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11
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Jacobson MH, Ghassabian A, Gore AC, Trasande L. Exposure to environmental chemicals and perinatal psychopathology. Biochem Pharmacol 2022; 195:114835. [PMID: 34774531 PMCID: PMC8712457 DOI: 10.1016/j.bcp.2021.114835] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 11/05/2021] [Accepted: 11/08/2021] [Indexed: 01/03/2023]
Abstract
Women are nearly twice as likely to develop mood disorders compared with men, and incidence is greatest during reproductive transitions, including pregnancy and postpartum. Because these periods are characterized by dramatic hormonal and physiologic changes, there is heightened susceptibility to external factors, such as exposure to environmental toxicants, which may play a role in maternal psychopathology. The purpose of this scoping review was to provide an overview of studies conducted in humans and animal models on the effects of nonoccupational exposure to environmental chemicals on maternal psychopathology during the perinatal period. The largest number of studies examined exposure to environmental tobacco smoke and antenatal depression and showed consistently positive findings, although more prospective studies using biomarkers for exposure assessment are needed. The few studies examining persistent organic pollutants such as polybrominated diphenyl ethers and perinatal depression were consistent in showing associations with increased depressive symptoms. Results were mixed for exposure to heavy metals and non-persistent chemicals, but a strong literature in animal models supported an association between bisphenols and phthalates and reduced maternal behavior and care of pups after parturition. Biological mechanisms may include endocrine disruption, neurotransmitter system impairment, alterations in gene expression, and immune activation and inflammation. Additional longitudinal studies that include biospecimen collection are essential to furthering the understanding of how environmental toxicants during pregnancy may affect perinatal psychopathology and the underlying mechanisms of action. Future work should also leverage the parallels between animal and human maternal behavior, thereby highlighting the opportunity for multidisciplinary work in this avenue.
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Affiliation(s)
- Melanie H Jacobson
- Department of Pediatrics, New York University Grossman School of Medicine, New York, NY, USA.
| | - Akhgar Ghassabian
- Department of Pediatrics, New York University Grossman School of Medicine, New York, NY, USA; Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, USA; Department of Population Health, New York University Grossman School of Medicine, New York, NY, USA
| | - Andrea C Gore
- Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, USA; Division of Pharmacology & Toxicology, The University of Texas at Austin, Austin, TX 78712, USA
| | - Leonardo Trasande
- Department of Pediatrics, New York University Grossman School of Medicine, New York, NY, USA; Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, USA; Department of Population Health, New York University Grossman School of Medicine, New York, NY, USA; New York University Wagner School of Public Service, New York, NY, USA; New York University College of Global Public Health, New York, NY, USA
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12
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Simpson RJ, Boßlau TK, Weyh C, Niemiro GM, Batatinha H, Smith KA, Krüger K. Exercise and adrenergic regulation of immunity. Brain Behav Immun 2021; 97:303-318. [PMID: 34302965 DOI: 10.1016/j.bbi.2021.07.010] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 06/07/2021] [Accepted: 07/16/2021] [Indexed: 12/14/2022] Open
Abstract
Exercise training has a profound impact on immunity, exerting a multitude of positive effects in indications such as immunosenescence, cancer, viral infections and inflammatory diseases. The immune, endocrine and central nervous systems work in a highly synergistic manner and it has become apparent that catecholamine signaling through leukocyte β-adrenergic receptors (β-ARs) is a key mechanism by which exercise mediates improvements in immune function to help mitigate numerous disease conditions. Central to this is the preferential mobilization and redistribution of effector lymphocytes with potent anti-viral and anti-tumor activity, their interaction with muscle-derived cytokines, and the effects of catecholamine signaling on mitochondrial biogenesis, immunometabolism and the resulting inflammatory response. Here, we review the impact of acute and chronic exercise on adrenergic regulation of immunity in the context of aging, cancer, viral infections and inflammatory disease. We also put forth our contention that exercise interventions designed to improve immunity, prevent disease and reduce inflammation should consider the catecholamine-AR signaling axis as a therapeutic target and ask whether or not the adrenergic signaling machinery can be 'trained' to improve immune responses to stress, disease or during the normal physiological process of aging. Finally, we discuss potential strategies to augment leukocyte catecholamine signaling to boost the effects of exercise on immunity in individuals with desensitized β-ARs or limited exercise tolerance.
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Affiliation(s)
- Richard J Simpson
- University of Arizona, Department of Nutritional Sciences, Tucson, AZ, USA; University of Arizona, Department of Pediatrics, Tucson, AZ, USA; University of Arizona, Department of Immunobiology, Tucson, AZ, USA; University of Arizona Cancer Center, Tucson, AZ, USA.
| | - Tim K Boßlau
- University of Gießen, Department of Exercise Physiology and Sports Therapy, Gießen, Germany
| | - Christopher Weyh
- University of Gießen, Department of Exercise Physiology and Sports Therapy, Gießen, Germany
| | - Grace M Niemiro
- University of Arizona, Department of Pediatrics, Tucson, AZ, USA; University of Arizona Cancer Center, Tucson, AZ, USA
| | - Helena Batatinha
- University of Arizona, Department of Pediatrics, Tucson, AZ, USA
| | - Kyle A Smith
- University of Arizona, Department of Nutritional Sciences, Tucson, AZ, USA; University of Arizona, Department of Pediatrics, Tucson, AZ, USA
| | - Karsten Krüger
- University of Gießen, Department of Exercise Physiology and Sports Therapy, Gießen, Germany.
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13
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Fleszar MG, Fortuna P, Zawadzki M, Hodurek P, Bednarz-Misa I, Witkiewicz W, Krzystek-Korpacka M. Sex, Type of Surgery, and Surgical Site Infections Are Associated with Perioperative Cortisol in Colorectal Cancer Patients. J Clin Med 2021; 10:jcm10040589. [PMID: 33557291 PMCID: PMC7914878 DOI: 10.3390/jcm10040589] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 01/19/2021] [Accepted: 02/01/2021] [Indexed: 12/24/2022] Open
Abstract
Excessive endocrine response to trauma negatively affects patients’ well-being. Cortisol dynamics following robot-assisted colorectal surgery are unknown. We aimed at determining the impact of cancer pathology and surgery-related factors on baseline cortisol levels and analyzed its time-profile in colorectal cancer patients undergoing open or robot-assisted surgery. Cortisol levels were measured using liquid chromatography quadrupole time-of-flight mass spectrometry. Baseline cortisol was not associated with any patient- or disease-related factors. Post-surgery cortisol increased by 36% at 8 h and returned to baseline on postoperative day three. The cortisol time profile was significantly affected by surgery type, estimated blood loss, and length of surgery. Baseline-adjusted cortisol increase was greater in females at hour 8 and in both females and patients from open surgery group at hour 24. Solely in the open surgery group, cortisol dynamics paralleled changes in interleukin (IL)-1β, IL-10, IL-1ra, IL-7, IL-8 and tumor necrosis factor (TNF)-α but did not correlate with changes in IL-6 or interferon (IFN)-γ at any time-point. Cortisol co-examined with C-reactive protein was predictive of surgical site infections (SSI) with high accuracy. In conclusion, patient’s sex and surgery invasiveness affect cortisol dynamics. Surgery-induced elevation can be reduced by minimally invasive robot-assisted procedures. Cortisol and C-reactive protein as SSI biomarkers might be of value in the evaluation of safety of early discharge of patients.
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Affiliation(s)
- Mariusz G. Fleszar
- Department of Medical Biochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland; (M.G.F.); (P.F.); (P.H.); (I.B.-M.)
| | - Paulina Fortuna
- Department of Medical Biochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland; (M.G.F.); (P.F.); (P.H.); (I.B.-M.)
| | - Marek Zawadzki
- Department of Oncological Surgery, Regional Specialist Hospital, 51-124 Wroclaw, Poland; (M.Z.); (W.W.)
- Department of Physiotherapy, Wroclaw Medical University, 51-618 Wroclaw, Poland
| | - Paweł Hodurek
- Department of Medical Biochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland; (M.G.F.); (P.F.); (P.H.); (I.B.-M.)
| | - Iwona Bednarz-Misa
- Department of Medical Biochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland; (M.G.F.); (P.F.); (P.H.); (I.B.-M.)
| | - Wojciech Witkiewicz
- Department of Oncological Surgery, Regional Specialist Hospital, 51-124 Wroclaw, Poland; (M.Z.); (W.W.)
- Research and Development Centre at Regional Specialist Hospital, 51-124 Wroclaw, Poland
| | - Małgorzata Krzystek-Korpacka
- Department of Medical Biochemistry, Wroclaw Medical University, 50-368 Wroclaw, Poland; (M.G.F.); (P.F.); (P.H.); (I.B.-M.)
- Correspondence: ; Tel.: +48-71-784-1375
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14
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Rostagno MH. Effects of heat stress on the gut health of poultry. J Anim Sci 2020; 98:5811133. [PMID: 32206781 DOI: 10.1093/jas/skaa090] [Citation(s) in RCA: 101] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 03/20/2020] [Indexed: 12/14/2022] Open
Abstract
Stress is a biological adaptive response to restore homeostasis, and occurs in every animal production system, due to the multitude of stressors present in every farm. Heat stress is one of the most common environmental challenges to poultry worldwide. It has been extensively demonstrated that heat stress negatively impacts the health, welfare, and productivity of broilers and laying hens. However, basic mechanisms associated with the reported effects of heat stress are still not fully understood. The adaptive response of poultry to a heat stress situation is complex and intricate in nature, and it includes effects on the intestinal tract. This review offers an objective overview of the scientific evidence available on the effects of the heat stress response on different facets of the intestinal tract of poultry, including its physiology, integrity, immunology, and microbiota. Although a lot of knowledge has been generated, many gaps persist. The development of standardized models is crucial to be able to better compare and extrapolate results. By better understanding how the intestinal tract is affected in birds subjected to heat stress conditions, more targeted interventions can be developed and applied.
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15
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Te Pas MFW, Borg R, Buddiger NJH, Wood BJ, Rebel JMJ, van Krimpen MM, Calus MPL, Park JE, Schokker D. Regulating appetite in broilers for improving body and muscle development - A review. J Anim Physiol Anim Nutr (Berl) 2020; 104:1819-1834. [PMID: 32592266 PMCID: PMC7754290 DOI: 10.1111/jpn.13407] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 05/27/2020] [Accepted: 05/28/2020] [Indexed: 12/12/2022]
Abstract
Appetite is the desire for feed and water and the voluntary intake of feed and is an important regulator of livestock productivity and animal health. Economic traits such as growth rate and muscle development (meat deposition) in broilers are directly correlated to appetite. Factors that may influence appetite include environmental factors, such as stress and temperature variation, and animal‐specific factors, such as learning period, eating capacity and preferences. Feed preferences have been reported to be determined in early life, and this period is important in broilers due to their fast growth and relatively short growth trajectories. This may be of importance when contemplating the use of more circular and sustainable feeds and the optimization of appetite for these feeds. The objective of this review was to review the biological mechanisms underlying appetite using data from human, animal and bird models and to consider the option for modulating appetite particularly as it relates to broiler chickens.
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Affiliation(s)
- Marinus F W Te Pas
- Wageningen University and Research, Wageningen Livestock Research, Wageningen, The Netherlands
| | | | | | - Benjamin J Wood
- Hendrix Genetics North America Office, Kitchener, ON, Canada
| | - Johanna M J Rebel
- Wageningen University and Research, Wageningen Livestock Research, Wageningen, The Netherlands
| | - Marinus M van Krimpen
- Wageningen University and Research, Wageningen Livestock Research, Wageningen, The Netherlands
| | - Mario P L Calus
- Wageningen University and Research, Wageningen Livestock Research, Wageningen, The Netherlands
| | - Jong-Eun Park
- Animal Genomics & Bioinformatics Division, National Institute of Animal Science, Rural Development Administration, Jeonju, Korea
| | - Dirkjan Schokker
- Wageningen University and Research, Wageningen Livestock Research, Wageningen, The Netherlands
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16
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Batt MM, Duffy KA, Novick AM, Metcalf CA, Epperson CN. Is Postpartum Depression Different From Depression Occurring Outside of the Perinatal Period? A Review of the Evidence. FOCUS (AMERICAN PSYCHIATRIC PUBLISHING) 2020; 18:106-119. [PMID: 33162848 PMCID: PMC7587887 DOI: 10.1176/appi.focus.20190045] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Whether a major depressive episode occurring in the postpartum period (i.e., postpartum depression [PPD]) is sufficiently distinct from major depressive episodes occurring at other times (i.e., major depressive disorder) to warrant a separate diagnosis is a point of debate with substantial clinical significance. The evidence for and against diagnostic distinction for PPD is reviewed with respect to epidemiology, etiology, and treatment. Overall, evidence that PPD is distinct from major depressive disorder is mixed and is largely affected by how the postpartum period is defined. For depression occurring in the early postpartum period (variably defined, but typically with onset in the first 8 weeks), symptom severity, heritability, and epigenetic data suggest that PPD may be distinct, whereas depression occurring in the later postpartum period may be more similar to major depressive disorder occurring outside of the perinatal period. The clinical significance of this debate is considerable given that PPD, the most common complication of childbirth, is associated with immediate and enduring adverse effects on maternal and offspring morbidity and mortality. Future research investigating the distinctiveness of PPD from major depressive disorder in general should focus on the early postpartum period when the rapid decline in hormones contributes to a withdrawal state, requiring profound adjustments in central nervous system function.
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Affiliation(s)
- Melissa M Batt
- Department of Psychiatry (all authors) and Helen and Arthur E. Johnson Depression Center (Batt), University of Colorado School of Medicine, Anschutz Medical Campus, Aurora
| | - Korrina A Duffy
- Department of Psychiatry (all authors) and Helen and Arthur E. Johnson Depression Center (Batt), University of Colorado School of Medicine, Anschutz Medical Campus, Aurora
| | - Andrew M Novick
- Department of Psychiatry (all authors) and Helen and Arthur E. Johnson Depression Center (Batt), University of Colorado School of Medicine, Anschutz Medical Campus, Aurora
| | - Christina A Metcalf
- Department of Psychiatry (all authors) and Helen and Arthur E. Johnson Depression Center (Batt), University of Colorado School of Medicine, Anschutz Medical Campus, Aurora
| | - C Neill Epperson
- Department of Psychiatry (all authors) and Helen and Arthur E. Johnson Depression Center (Batt), University of Colorado School of Medicine, Anschutz Medical Campus, Aurora
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17
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Wang Y, Xia L, Guo T, Heng C, Jiang L, Wang D, Wang J, Li K, Zhan X. Research Note: Metabolic changes and physiological responses of broilers in the final stage of growth exposed to different environmental temperatures. Poult Sci 2020; 99:2017-2025. [PMID: 32241486 PMCID: PMC7587865 DOI: 10.1016/j.psj.2019.11.048] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 11/14/2019] [Accepted: 11/15/2019] [Indexed: 11/28/2022] Open
Abstract
There is no information regarding the influence of heat stress (HS) on host metabolic profile. In this study, we investigated the effects of different environmental temperatures on oxidative status, hormone levels, HS indicators, and plasma metabolites in broilers. A total of 1,680 yellow-feather broilers (28 D old) were randomly allotted to 4 groups with 6 replicates. The broilers (29–57 D old) were maintained in thermostatic rooms (20°C, 25°C, 28°C, and 30°C) for 28 consecutive days. The results showed that the plasma cortisol and adrenocorticotropic hormone levels and creatine kinase and lactate dehydrogenase activities gradually increased when the temperature increased from 20°C to 30°C. However, the insulin-like growth factor-І level decreased gradually. Furthermore, heat shock protein 70 expression significantly increased in the liver and breast muscle (P < 0.01). As the temperature increased, the total anti-oxidant capacity in the plasma and liver gradually decreased, whereas the malondialdehyde level increased. The activity of plasma glutathione peroxidase and total superoxide dismutase in the liver showed a similar increasing trend (P < 0.01). In addition, 15 metabolites were identified at higher (P < 0.05) levels, whereas 2 metabolites were identified at lower (P < 0.05) levels in the 30°C treatment group than those in the 25°C treatment group. Most of these potentially diagnostic biomarkers are involved in carbohydrate, amino acid, lipid, or gut microbiome-derived metabolism, indicating that HS affected the metabolic pathways in broilers. Six candidate metabolites (tartronic acid, l-bethreine, tartaric acid, allose, glutaric acid, and neohesperidin) were selected as biomarkers, as they showed high sensitivity, specificity, and accuracy in diagnosing broilers under HS (P < 0.01). In conclusion, in the final stage of growth, we identified 6 plasma differential metabolites as potential biomarkers of HS-induced metabolic disorders in yellow-feathered broilers. This work offers new insights into the metabolic alterations of broilers exposed to HS and provides a new perspective for further study.
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Affiliation(s)
- Yuanyuan Wang
- College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Lei Xia
- Agricultural Product Quality and Safety Management Center, Zhoushan, China
| | - Tianyu Guo
- College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Chianning Heng
- College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Lei Jiang
- College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Dianchun Wang
- College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Jiangshui Wang
- College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Kaixuan Li
- College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Xiuan Zhan
- College of Animal Sciences, Zhejiang University, Hangzhou, China.
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18
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Ramspacher A, Neudert M, Koller A, Schlager S, Kofler B, Brunner SM. Influence of the regulatory peptide galanin on cytokine expression in human monocytes. Ann N Y Acad Sci 2019; 1455:185-195. [PMID: 31074091 PMCID: PMC6899851 DOI: 10.1111/nyas.14111] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 03/27/2019] [Accepted: 04/05/2019] [Indexed: 01/08/2023]
Abstract
Current research into neuropeptides is bringing to light many remarkable functions of these endocrine/neurocrine/paracrine factors, such as their roles in modulating immune responses. Galanin is a neuropeptide expressed in both neural and non‐neural tissues and exerts its effects through three G protein–coupled receptors, GAL1,2,3‐R. It has been demonstrated that galanin has modulatory effects on immune cells, including neutrophils and natural killer cells. Because monocytes express GAL2‐R, and therefore are expected to be a target of galanin, we analyzed the effect of galanin on the expression of cytokines and chemokines by monocytes. Galanin increased the expression of IL‐1β up to 1.5‐fold, TNF‐α, IL‐10, IL‐18, and CCL3 up to twofold, and CXCL8 up to fourfold in nonactivated monocytes, but had no major effect on activated monocytes. A cross‐correlation analysis of cytokine expression profiles, irrespective of the activation status of the monocytes, revealed that galanin changed the cross‐correlation of the expression of certain cytokines. Galanin abolished several significant correlations in IFN‐γ–stimulated monocytes. For example, treatment with 10 nM galanin changed the Spearman's rank coefficient of IL‐18 and CXCL8 from 0.622 (P ≤ 0.01) to 0.126. These results further emphasize the importance of neuroregulatory peptides, such as galanin and their therapeutic potential to treat inflammatory diseases.
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Affiliation(s)
- Andrea Ramspacher
- Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Salzburg, Austria
| | - Magdalena Neudert
- Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Salzburg, Austria
| | - Andreas Koller
- Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Salzburg, Austria.,University Clinic of Ophthalmology and Optometry, Research Program for Ophthalmology and Glaucoma Research, University Hospital of the Paracelsus Medical University, Salzburg, Austria
| | - Sandra Schlager
- Department of Blood Group Serology and Transfusion Medicine, University Hospital of the Paracelsus Medical University, Salzburg, Austria
| | - Barbara Kofler
- Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Salzburg, Austria
| | - Susanne Maria Brunner
- Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Salzburg, Austria
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19
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Galanin is a potent modulator of cytokine and chemokine expression in human macrophages. Sci Rep 2019; 9:7237. [PMID: 31076613 PMCID: PMC6510899 DOI: 10.1038/s41598-019-43704-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2018] [Accepted: 04/26/2019] [Indexed: 12/14/2022] Open
Abstract
The regulatory peptide galanin is broadly distributed in the central- and peripheral nervous systems as well as in non-neuronal tissues, where it exerts its diverse physiological functions via three G-protein-coupled receptors (GAL1-3-R). Regulatory peptides are important mediators of the cross-communication between the nervous- and immune systems and have emerged as a focus of new therapeutics for a variety of inflammatory diseases. Studies on inflammatory animal models and immune cells revealed both pro- and anti-inflammatory functions of galanin. Here, we probed specific immune-related functions of the galanin system and found galanin and GAL1-R and GAL2-R mRNA to be expressed in a range of human immune cells. In particular, macrophages displayed differentiation- and polarization-dependent expression of galanin and its receptors. Exposure to exogenous galanin affected the cytokine/chemokine expression profile of macrophages differently, depending on their differentiation and polarization, and mainly modulated the expression of chemokines (CCL2, CCL3, CCL5 and CXCL8) and anti-inflammatory cytokines (TGF-β, IL-10 and IL-1Ra), especially in type-1 macrophages. Cytokine/chemokine expression levels in interferon-gamma- and lipopolysaccharide-polarized macrophages were upregulated whereas in unpolarized macrophages they were downregulated upon galanin treatment for 20 hours. This study illuminates the regulation of important cytokines/chemokines in macrophages by galanin, depending on specific cell activation.
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20
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Rodríguez Bustos H, Espinoza-Navarro O, Castro ME. Effect of classical conditioning over immature and mature B lymphocytes regulation. Microsc Res Tech 2018; 81:1451-1455. [PMID: 30365190 DOI: 10.1002/jemt.23112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Revised: 06/11/2018] [Accepted: 07/23/2018] [Indexed: 11/09/2022]
Abstract
Classical conditioning (CC) with a sweet flavored is useful for experimental models of immune response. The objective this work was analyze spleen cell response on the differentiation of B-lymphocytes associated with the CC with sweet flavored in adult rats. Twelve adult male rats were divided (n = 3) in Group 1 (control); Group 2 without conditioned stimulus (WCS) received only water; Group 3 receiving only water with salt; Group 4 (experimental) with CS of sweet flavored and salty flavored afterwards. In every work group, all animals were subjected to the unconditioned stimulus (US) treated by 10 mg/kg body weight of cyclophosphamide injected intraperitoneally (i.p.). Subsequently an immunological challenge with sheep red blood cells i.p. was applied. Spleen samples were obtained 15 days after using euthanasia with 1% sodium thiopental i.p. The evaluation B lymphocyte (immature and mature) was performed by immunohistochemistry using specific antibodies against CD20 and against CD37, and revealed with HRP/DAB. The results show in every work group significant increases of CD20+ and CD37+ cell densities in the red pulp of the spleen of male adult rats from different groups of the experimental design. We concluded that the immunomodulatory response under CC might facilitate a less aggressive and more physiological immunological response against immunosuppression. RESEARCH HIGHLIGHTS: The immune response can be reinforced by classical conditioning. The sweet taste allows to positively condition the immune response. B lymphocytes actively participate in the immune response and classical conditioning.
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Affiliation(s)
- Héctor Rodríguez Bustos
- Laboratory of Morphology, Anatomy and Development of Biology, Faculty of Medicine, University of Chile, Santiago, Chile
| | - Omar Espinoza-Navarro
- Laboratory of Morphology, Anatomy and Development of Biology, Faculty of Medicine, University of Chile, Santiago, Chile
| | - María Eugenia Castro
- Laboratory of Morphology, Anatomy and Development of Biology, Faculty of Medicine, University of Chile, Santiago, Chile
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21
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Qin Y, Smith TG, Jackson F, Gallardo-Romero NF, Morgan CN, Olson V, Hutson CL, Wu X. Revisiting rabies virus neutralizing antibodies through infecting BALB/c mice with live rabies virus. Virus Res 2018; 248:39-43. [PMID: 29471052 DOI: 10.1016/j.virusres.2018.02.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Revised: 02/02/2018] [Accepted: 02/12/2018] [Indexed: 12/24/2022]
Abstract
This study investigates the production of rabies virus (RABV) neutralizing antibody after virus infection through a mouse model. The BALB/c mice from different age groups (three, five, seven week old) were intramuscularly inoculated with live rabies virus (TX coyote 323R). Without pre-exposure or post-exposure prophylaxis (PEP), we found there is a decreased fatality with increased age of animals, the mortalities are 60%, 50%, and 30%, respectively. Interestingly, through assay of rapid fluorescent focus inhibition test (RFFIT), direct fluorescent antibody (DFA) and quantitative Polymerase Chain Reaction (qPCR), the results showed that all the animals that succumbed to rabies challenge, except one, developed circulating neutralizing antibodies, and all the healthy animals, except two, did not generate virus neutralizing antibodies (VNA). Our animal study suggests that the induction of VNA was an indicator of infection progression in the central nervous system (CNS) and speculate that RABV neutralizing antibodies did not cross the blood-brain barrier of the CNS for those diseased animals. We hypothesize that early release of viral antigens from damaged nerve tissue might potentially be a benefit for survivors, and we also discuss several other aspects of the interaction of RABV and its neutralizing antibodies.
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Affiliation(s)
- Yunlong Qin
- Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, USA; Chronic Viral Diseases Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, USA.
| | - Todd G Smith
- Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, USA
| | - Felix Jackson
- Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, USA
| | - Nadia F Gallardo-Romero
- Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, USA
| | - Clint N Morgan
- Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, USA
| | - Victoria Olson
- Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, USA
| | - Christina L Hutson
- Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, USA.
| | - Xianfu Wu
- Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, USA
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22
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Neuman‐Lee LA, Terletzky PA, Atwood TC, Gese EM, Smith GD, Greenfield S, Pettit J, French SS. Demographic and temporal variations in immunity and condition of polar bears (
Ursus maritimus
) from the southern Beaufort Sea. JOURNAL OF EXPERIMENTAL ZOOLOGY PART 2017; 327:333-346. [DOI: 10.1002/jez.2112] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Revised: 08/27/2017] [Accepted: 08/29/2017] [Indexed: 11/09/2022]
Affiliation(s)
| | | | - Todd C. Atwood
- U.S. Geological Survey Alaska Science Center Anchorage Alaska
| | - Eric M. Gese
- Department of Wildland Resources Utah State University Logan Utah
- U.S. Department of Agriculture Wildlife Services National Wildlife Research Center Logan Utah
| | - Geoffrey D. Smith
- Department of Biological Sciences Dixie State University St. George Utah
| | | | - John Pettit
- Department of Biology Utah State University Logan Utah
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23
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Stress Induced Polarization of Immune-Neuroendocrine Phenotypes in Gallus gallus. Sci Rep 2017; 7:8102. [PMID: 28808318 PMCID: PMC5556001 DOI: 10.1038/s41598-017-08733-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Accepted: 07/14/2017] [Indexed: 12/11/2022] Open
Abstract
Immune-neuroendocrine phenotypes (INPs) stand for population subgroups differing in immune-neuroendocrine interactions. While mammalian INPs have been characterized thoroughly in rats and humans, avian INPs were only recently described in Coturnix coturnix (quail). To assess the scope of this biological phenomenon, herein we characterized INPs in Gallus gallus (a domestic hen strain submitted to a very long history of strong selective breeding pressure) and evaluated whether a social chronic stress challenge modulates the individuals' interplay affecting the INP subsets and distribution. Evaluating plasmatic basal corticosterone, interferon-γ and interleukin-4 concentrations, innate/acquired leukocyte ratio, PHA-P skin-swelling and induced antibody responses, two opposite INP profiles were found: LEWIS-like (15% of the population) and FISCHER-like (16%) hens. After chronic stress, an increment of about 12% in each polarized INP frequency was found at expenses of a reduction in the number of birds with intermediate responses. Results show that polarized INPs are also a phenomenon occurring in hens. The observed inter-individual variation suggest that, even after a considerable selection process, the population is still well prepared to deal with a variety of immune-neuroendocrine challenges. Stress promoted disruptive effects, leading to a more balanced INPs distribution, which represents a new substrate for challenging situations.
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24
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Koller A, Bianchini R, Schlager S, Münz C, Kofler B, Wiesmayr S. The neuropeptide galanin modulates natural killer cell function. Neuropeptides 2017; 64:109-115. [PMID: 27837916 DOI: 10.1016/j.npep.2016.11.002] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Accepted: 11/01/2016] [Indexed: 12/20/2022]
Abstract
Natural killer (NK) cells are part of the innate immune system and combat pathogens and tumors by secreting pro-inflammatory cytokines like interferon gamma (IFN-γ) and by their cytotoxic action. Galanin is a neuropeptide also expressed in peripheral tissue where it impacts several physiological functions, including inflammation. The effects of galanin are mediated via three receptors, GAL1-3. Since other neuropeptides have been shown to regulate NK cell activity, we investigated the potential of galanin to modulate human NK cell function. NK cells were isolated from human peripheral blood mononuclear cells. mRNA expression was analyzed by qRT-PCR. The dynamic mass redistribution of NK cells upon regulatory peptide stimulation was determined by label-free biochip technology. IFN-γ producing NK cells were identified by flow cytometry analysis and IFN-γ secretion was measured by ELISA. NK cell cytotoxicity was analyzed by flow cytometry via CD107a mobilization. NK cells were found to express the receptor GAL2 but not GAL1, GAL3 or galanin. Galanin per se did not affect the dynamic mass redistribution of NK cells, but significantly enhanced the response of NK cells to IL-18. Galanin significantly modulated the IFN-γ production of the CD56bright NK cell population upon IL-12 and IL-18 stimulation. Furthermore, galanin significantly modulated the IL-12 and IL-18 stimulated IFN-γ secretion. NK cell cytotoxicity was not modulated by galanin treatment. Galanin can be classified as an immunomodulatory peptide as it is able to sensitize NK cells toward specific cytokines.
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Affiliation(s)
- Andreas Koller
- Laura Bassi Centre of Expertise THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria
| | - Rodolfo Bianchini
- Laura Bassi Centre of Expertise THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria
| | - Sandra Schlager
- Department of Blood Group Serology and Transfusion Medicine, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria
| | - Christian Münz
- Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Rämistraße 71, 8006 Zürich, Switzerland
| | - Barbara Kofler
- Laura Bassi Centre of Expertise THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria.
| | - Silke Wiesmayr
- Department of Neonatology, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria
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25
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The multiple adrenocorticotropic hormone injections significantly alters hepatic proteome in growing pigs. Livest Sci 2017. [DOI: 10.1016/j.livsci.2017.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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26
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Ngo Ndjom CG, Kantor LV, Jones HP. CRH Affects the Phenotypic Expression of Sepsis-Associated Virulence Factors by Streptococcus pneumoniae Serotype 1 In vitro. Front Cell Infect Microbiol 2017; 7:263. [PMID: 28690980 PMCID: PMC5479890 DOI: 10.3389/fcimb.2017.00263] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Accepted: 06/02/2017] [Indexed: 12/20/2022] Open
Abstract
Sepsis is a life-threatening health condition caused by infectious pathogens of the respiratory tract, and accounts for 28–50% of annual deaths in the US alone. Current treatment regimen advocates the use of corticosteroids as adjunct treatment with antibiotics, for their broad inhibitory effect on the activity and production of pro-inflammatory mediators. However, despite their use, corticosteroids have not proven to be able to reverse the death incidence among septic patients. We have previously demonstrated the potential for neuroendocrine factors to directly influence Streptococcus pneumoniae virulence, which may in turn mediate disease outcome leading to sepsis and septic shock. The current study investigated the role of Corticotropin-releasing hormone (CRH) in mediating key markers of pneumococcal virulence as important phenotypic determinants of sepsis and septic shock risks. In vitro cultures of serotype 1 pneumococcal strain with CRH promoted growth rate, increased capsule thickness and penicillin resistance, as well as induced pneumolysin gene expression. These results thus provide significant insights of CRH–pathogen interactions useful in understanding the underlying mechanisms of neuroendocrine factor's role in the onset of community acquired pneumonias (CAP), sepsis and septic shock.
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Affiliation(s)
- Colette G Ngo Ndjom
- Department of Molecular and Medical Genetics, University of North Texas Health Science CenterFort Worth, TX, United States
| | - Lindsay V Kantor
- Graduate School of Biomedical Sciences, University of North Texas Health Science CenterFort Worth, TX, United States
| | - Harlan P Jones
- Department of Molecular and Medical Genetics, University of North Texas Health Science CenterFort Worth, TX, United States
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27
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Neuman-Lee LA, French SS. Endocrine-reproductive-immune interactions in female and male Galápagos marine iguanas. Horm Behav 2017; 88:60-69. [PMID: 27818221 DOI: 10.1016/j.yhbeh.2016.10.017] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 10/25/2016] [Accepted: 10/28/2016] [Indexed: 12/14/2022]
Abstract
Endocrine-immune interactions are variable across species and contexts making it difficult to discern consistent patterns. There is a paucity of data in non-model systems making these relationships even more nebulous, particularly in reptiles. In the present study, we have completed a more comprehensive test of the relationship among steroid hormones and ecologically relevant immune measures. We tested the relationship between baseline and stress-induced levels of sex and adrenal steroid hormones and standard ecoimmunological metrics in both female and male Galápagos marine iguanas (Amblyrhynchus cristatus). We found significant associations between adrenal activity and immunity, whereby females that mounted greater corticosterone responses to stress had lower basal and stress-induced immunity (i.e., bactericidal ability). Males showed the opposite relationship, suggesting sex-specific immunomodulatory actions of corticosterone. In both sexes, we observed a stress-induced increase in corticosterone, and in females a stress-induced increase in bactericidal ability. Consistent with other taxa, we also found that baseline corticosterone and testosterone in males was inversely related to baseline bactericidal ability. However, in females, we found a positive relationship between both testosterone and progesterone and bactericidal ability. Multivariate analysis did not discern any further endocrine-immune relationships, suggesting that interactions between adrenal, sex steroid hormones, and the immune system may not be direct and instead may be responding to other common stimuli, (i.e., reproductive status, energy). Taken together, these data illustrate significant endocrine-immune interactions that are highly dependent on sex and the stress state of the animal.
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Affiliation(s)
- Lorin A Neuman-Lee
- Department of Biology, Utah State University, 5305 Old Main Hill, Logan, UT 84322-5305, USA; The Ecology Center, Utah State University, 5205 Old Main Hill, Logan, UT 84322-5205, USA
| | - Susannah S French
- Department of Biology, Utah State University, 5305 Old Main Hill, Logan, UT 84322-5305, USA; The Ecology Center, Utah State University, 5205 Old Main Hill, Logan, UT 84322-5205, USA.
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28
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Harricharan R, Abboussi O, Daniels WM. Addiction: A dysregulation of satiety and inflammatory processes. PROGRESS IN BRAIN RESEARCH 2017; 235:65-91. [DOI: 10.1016/bs.pbr.2017.07.012] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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29
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Papathanassoglou EDE, Middleton N, Hegadoren K. Sex-dependent disparities in critical illness: methodological implications for critical care research. Nurs Crit Care 2016; 20:58-62. [PMID: 25704543 DOI: 10.1111/nicc.12166] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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30
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The choroid plexus in health and in disease: dialogues into and out of the brain. Neurobiol Dis 2016; 107:32-40. [PMID: 27546055 DOI: 10.1016/j.nbd.2016.08.011] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Revised: 07/20/2016] [Accepted: 08/17/2016] [Indexed: 12/31/2022] Open
Abstract
This article brings the choroid plexus into the context of health and disease. It is remarkable that the choroid plexus, composed by a monolayer of epithelial cells that lie in a highly vascularized stroma, floating within the brain ventricles, gets so little attention in major physiology and medicine text books and in the scientific literature in general. Consider that it is responsible for producing most of the about 150mL of cerebrospinal fluid that fills the brain ventricles and the subarachnoid space and surrounds the spinal cord in the adult human central nervous system, which is renewed approximately 2-3 times daily. As such, its activity influences brain metabolism and function, which will be addressed. Reflect that it contains an impressive number of receptors and transporters, both in the apical and basolateral sides of the epithelial cells, and as such is a key structure for the communication between the brain and the periphery. This will be highlighted in the context of neonatal jaundice, multiple sclerosis and Alzheimer's disease. Realize that the capillaries that irrigate the choroid plexus stroma do not possess tight junctions and that the blood flow to the choroid plexus is five times higher than that in the brain parenchyma, allowing for a rapid sensing system and delivery of molecules such as nutrients and metals as will be revised. Recognize that certain drugs reach the brain parenchyma solely through the choroid plexus epithelia, which has potential to be manipulated in diseases such as neonatal jaundice and Alzheimer's disease as will be discussed. Without further notice, it must be now clear that understanding the choroid plexus is necessary for comprehending the brain and how the brain is modulated and modulates all other systems, in health and in disease. This review article intends to address current knowledge on the choroid plexus, and to motivate the scientific community to consider it when studying normal brain physiology and diseases of the central nervous system. It will guide the reader through several aspects of the choroid plexus in normal physiology, in diseases characteristic of various periods of life (newborns-kernicterus, young adults-multiple sclerosis and the elder-Alzheimer's disease), and how sex-differences may relate to disease susceptibility.
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31
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Lopes F, Graepel R, Reyes JL, Wang A, Petri B, McDougall JJ, Sharkey KA, McKay DM. Involvement of Mast Cells in α7 Nicotinic Receptor Agonist Exacerbation of Freund's Complete Adjuvant-Induced Monoarthritis in Mice. Arthritis Rheumatol 2016; 68:542-52. [PMID: 26314943 DOI: 10.1002/art.39411] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Accepted: 08/25/2015] [Indexed: 01/01/2023]
Abstract
OBJECTIVE Activation of antiinflammatory cholinergic (vagal) pathways can reduce inflammation, and in vitro studies support a pivotal role of α7 nicotinic acetylcholine receptors (α7-nAChR), macrophages, and T cells in these events. The aim of this study was to assess α7-nAChR agonists as an antiinflammatory treatment for Freund's complete adjuvant (CFA)-induced monoarthritis. METHODS Arthritis was induced by intraarticular injection of CFA unilaterally into the knee joints of mice. Animals were treated with α7-nAChR agonists (AR-R17779 or A844606), with or without antagonists (COG133 or methyllycaconitine), and joint inflammation and pain were assessed. Experiments were repeated in c-Kit(W-sh) mast cell-deficient mice, and the effects of an α7-nAChR agonist on mast cell proliferation, migration, and activation by lipopolysaccharide (LPS) were tested. RESULTS Treatment with α7-nAChR agonists significantly exacerbated CFA-induced arthritis and pain, as gauged by all indices of assessment, the specificity of which was confirmed by coadministration of an nAChR antagonist that attenuated the increase in disease severity. Toluidine blue-positive mast cells were increased in the joint capsule of CFA plus AR-R17779-treated mice, and AR-R17779 enhanced LPS-induced TNF proliferation and migration of a human mast cell line. The AR-R17779-driven increase in severity of CFA-induced arthritis was significantly reduced in mast cell-deficient mice. CONCLUSION Using CFA to elicit a local inflammatory response, we found that pharmacologic activation of α7-nAChR exacerbated joint inflammation and pain, in part via mast cells, which illustrates the organ- and disease-specific nature of regulatory neuroimmune mechanisms. Thus, α7-nAChR activation may not be uniformly antiinflammatory in all types of inflammatory joint disease.
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Affiliation(s)
| | | | | | - Arthur Wang
- University of Calgary, Calgary, Alberta, Canada
| | - Björn Petri
- University of Calgary, Calgary, Alberta, Canada
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32
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Fernando F, Keijser R, Henneman P, van der Kevie-Kersemaekers AMF, Mannens MM, van der Post JA, Afink GB, Ris-Stalpers C. The idiopathic preterm delivery methylation profile in umbilical cord blood DNA. BMC Genomics 2015; 16:736. [PMID: 26419829 PMCID: PMC4588235 DOI: 10.1186/s12864-015-1915-4] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Accepted: 09/09/2015] [Indexed: 01/23/2023] Open
Abstract
BACKGROUND Preterm delivery is the leading cause of neonatal morbidity and mortality. Two-thirds of preterm deliveries are idiopathic. The initiating molecular mechanisms behind spontaneous preterm delivery are unclear. Umbilical cord blood DNA samples are an easy source of material to study the neonatal state at birth. DNA methylation changes can be exploited as markers to identify spontaneous preterm delivery. To identify methylation differences specific to idiopathic preterm delivery, we assessed genome-wide DNA methylation changes in 24 umbilical cord blood samples (UCB) using the 450 K Illumina methylation array. After quality control, conclusions were based on 11 term and 11 idiopathic preterm born neonates. The differentially methylated positions (DMPs) specific for preterm/term delivery, neonatal sex, use of oxytocin and mode of initiation of labor were calculated by controlling the FDR p value at 0.05. RESULTS The analysis identifies 1855 statistically significant DMPs between preterm and term deliveries of which 508 DMPs are also attributable to clinical variables other than preterm versus term delivery. 1347 DMPs are unique to term vs preterm delivery, of which 196 DMPs do not relate to gestational age as such. Pathway analysis indicated enrichment of genes involved in calcium signalling, myometrial contraction and relaxation pathways. The 1151 DMPs that correlate with advancing gestational age (p < 0.05) include 161 DMPs that match with two previously reported studies on UCB methylation. Additionally, 123 neonatal sex specific DMPs, 97 DMPs specific to the induction of labour and 42 DMPs specific to the mode of initiation of labor were also identified. CONCLUSION This study identifies 196 DMPs in UCB DNA of neonates which do not relate to gestational age or any other clinical variable recorded and are specific to idiopathic preterm delivery. Furthermore, 161 DMPs from our study overlap with previously reported studies of which a subset is also reported to be differentially methylated at 18 years of age. A DMP on MYL4, encoding myosin light chain 4, is a robust candidate for the identification of idiopathic preterm labour as it is identified by all 3 independent studies.
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Affiliation(s)
- Febilla Fernando
- Reproductive Biology Laboratory, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
| | - Remco Keijser
- Reproductive Biology Laboratory, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
| | - Peter Henneman
- Department of Clinical Genetics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
| | | | - Marcel Mam Mannens
- Department of Clinical Genetics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
| | - Joris Am van der Post
- Women's and Children's Clinic, Department of Obstetrics and Gynaecology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
| | - Gijs B Afink
- Reproductive Biology Laboratory, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
| | - Carrie Ris-Stalpers
- Reproductive Biology Laboratory, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. .,Women's and Children's Clinic, Department of Obstetrics and Gynaecology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
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Alamino VA, Montesinos MM, Rabinovich GA, Pellizas CG. The thyroid hormone triiodothyronine reinvigorates dendritic cells and potentiates anti-tumor immunity. Oncoimmunology 2015; 5:e1064579. [PMID: 26942081 DOI: 10.1080/2162402x.2015.1064579] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Accepted: 06/16/2015] [Indexed: 10/23/2022] Open
Abstract
Dendritic cell (DC) cancer vaccines have shown limited clinical benefit. Thus, the identification of signals and molecular pathways that potentiate the immunogenicity of DCs has become a major challenge in cancer research. Our studies demonstrate that triiodothyronine endows DCs with enhanced ability to stimulate cytotoxic T-cell responses with implications in DC-based immunotherapy.
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Affiliation(s)
- V A Alamino
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET) and Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba , Córdoba, Argentina
| | - M M Montesinos
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET) and Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba , Córdoba, Argentina
| | - G A Rabinovich
- Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME-CONICET) and Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Buenos Aires, Argentina
| | - C G Pellizas
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET) and Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba , Córdoba, Argentina
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Perrotta C, De Palma C, Clementi E, Cervia D. Hormones and immunity in cancer: are thyroid hormones endocrine players in the microglia/glioma cross-talk? Front Cell Neurosci 2015; 9:236. [PMID: 26157361 PMCID: PMC4477169 DOI: 10.3389/fncel.2015.00236] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Accepted: 06/11/2015] [Indexed: 11/16/2022] Open
Abstract
Accumulating evidence indicates that the endocrine and immune systems engage in complex cross-talks in which a prominent role is played by thyroid hormones (THs). The increase of resident vs. monocyte recruited macrophages was shown to be an important effector of the TH 3,3′,5′-Triiodo-L-thyronine (T3)-induced protection against inflammation and a key role of T3 in inhibiting the differentiation of peripheral monocytes into macrophages was observed. Herein, we report on the role of T3 as a modulator of microglia, the specialized macrophages of the central nervous system (CNS). Mounting evidence supports a role of microglia and macrophages in the growth and invasion of malignant glioma. In this respect, we unveil the putative involvement of T3 in the microglia/glioma cell communication. Since THs are known to cross the blood-brain barrier, we suggest that T3 not only exerts a direct modulation of brain cancer cell itself but also indirectly promotes glioma growth through a modulation of microglia. Our observations expand available information on the role of TH system in glioma and its microenvironment and highlight the endocrine modulation of microglia as an important target for future therapeutic development of glioma treatments.
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Affiliation(s)
- Cristiana Perrotta
- Department of Biomedical and Clinical Sciences "Luigi Sacco" (DIBIC), Unit of Clinical Pharmacology, National Research Council-Institute of Neuroscience, University Hospital "Luigi Sacco", Università di Milano Milano, Italy
| | - Clara De Palma
- Department of Biomedical and Clinical Sciences "Luigi Sacco" (DIBIC), Unit of Clinical Pharmacology, National Research Council-Institute of Neuroscience, University Hospital "Luigi Sacco", Università di Milano Milano, Italy
| | - Emilio Clementi
- Department of Biomedical and Clinical Sciences "Luigi Sacco" (DIBIC), Unit of Clinical Pharmacology, National Research Council-Institute of Neuroscience, University Hospital "Luigi Sacco", Università di Milano Milano, Italy ; Scientific Institute IRCCS Eugenio Medea Bosisio Parini, Italy
| | - Davide Cervia
- Department of Biomedical and Clinical Sciences "Luigi Sacco" (DIBIC), Unit of Clinical Pharmacology, National Research Council-Institute of Neuroscience, University Hospital "Luigi Sacco", Università di Milano Milano, Italy ; Department for Innovation in Biological, Agro-food and Forest Systems (DIBAF), Università della Tuscia, Largo dell'Università snc Viterbo, Italy
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35
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Liu Z, Zhou Z, Wang L, Jiang S, Wang W, Zhang R, Song L. The immunomodulation mediated by a delta-opioid receptor for [Met(5)]-enkephalin in oyster Crassostrea gigas. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2015; 49:217-224. [PMID: 25475959 DOI: 10.1016/j.dci.2014.11.017] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2014] [Revised: 11/25/2014] [Accepted: 11/25/2014] [Indexed: 06/04/2023]
Abstract
Opioid receptors (OR) are a group of G protein-coupled receptors with opioids as ligands, which play an important role in triggering the second messengers to modulate immune response in vertebrate immunocytes. In the present study, the full length cDNA of a homologue of δ-opioid receptor (DOR) for [Met(5)]-enkaphalin was cloned from oyster Crassostrea gigas (designated as CgDOR), which was 1104 bp encoding a peptide of 367 amino acids containing a conserved 7tm_1 domain. After the stimulation of [Met(5)]-enkephalin, the concentration of second messengers Ca(2+) and cAMP in the HEK293T cells decreased significantly (p <0.05) with the expression of CgDOR. However, this trend was reverted with the addition of DOR antagonist BNTX. The CgDOR transcripts were ubiquitously detected in the tested tissues including haemocytes, gonad, mantle, kidney, gill, adductor muscle and hepatopancreas, with the highest expression level in the hepatopancreas. After LPS stimulation, the expression level of CgDOR mRNA began to increase (4.05-fold, p <0.05) at 6 h, and reached the highest level (5.00-fold, p <0.05) at 12 h. Haemocyte phagocytic and antibacterial activities increased significantly after [Met(5)]-enkephalin stimulation, whereas the increase was repressed with the addition of DOR antagonist BNTX. These results collectively suggested that CgDOR for [Met(5)]-enkephalin could modulate the haemocyte phagocytic and antibacterial functions through the second messengers Ca(2+) and cAMP, which might be requisite for pathogen elimination and homeostasis maintenance in oyster.
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MESH Headings
- Amino Acid Sequence
- Animals
- Benzylidene Compounds/pharmacology
- Calcium/metabolism
- Cell Line
- Cloning, Molecular
- Crassostrea/immunology
- Cyclic AMP/metabolism
- DNA, Complementary/genetics
- Enkephalin, Methionine/immunology
- HEK293 Cells
- Hepatopancreas/metabolism
- Humans
- Lipopolysaccharides
- Molecular Sequence Data
- Naltrexone/analogs & derivatives
- Naltrexone/pharmacology
- Phagocytosis/immunology
- RNA, Messenger/biosynthesis
- Receptors, Opioid, delta/antagonists & inhibitors
- Receptors, Opioid, delta/genetics
- Receptors, Opioid, delta/immunology
- Sequence Alignment
- Signal Transduction/immunology
- Vibrio/immunology
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Affiliation(s)
- Zhaoqun Liu
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Zhi Zhou
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
| | - Lingling Wang
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
| | - Shuai Jiang
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
| | - Weilin Wang
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Ran Zhang
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; School of Marine Sciences, Ningbo University, Ningbo 315211, China
| | - Linsheng Song
- Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
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Nazar FN, Barrios BE, Kaiser P, Marin RH, Correa SG. Immune neuroendocrine phenotypes in Coturnix coturnix: do avian species show LEWIS/FISCHER-like profiles? PLoS One 2015; 10:e0120712. [PMID: 25793369 PMCID: PMC4368694 DOI: 10.1371/journal.pone.0120712] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Accepted: 01/26/2015] [Indexed: 12/23/2022] Open
Abstract
Immunoneuroendocrinology studies have identified conserved communicational paths in birds and mammals, e.g. the Hypothalamus-Pituitary-Adrenal axis with anti-inflammatory activity mediated by glucocorticoids. Immune neuroendocrine phenotypes (INPs) have been proposed for mammals implying the categorization of a population in subgroups underlying divergent immune-neuroendocrine interactions. These phenotypes were studied in the context of the LEWIS/FISCHER paradigm (rats expressing high or low pro-inflammatory profiles, respectively). Although avian species have some common immunological mechanisms with mammals, they have also evolved some distinct strategies and, until now, it has not been studied whether birds may also share with mammals similar INPs. Based on corticosterone levels we determined the existence of two divergent groups in Coturnix coturnix that also differed in other immune-neuroendocrine responses. Quail with lowest corticosterone showed higher lymphoproliferative and antibody responses, interferon-γ and interleukin-1β mRNA expression levels and lower frequencies of leukocyte subpopulations distribution and interleukin-13 levels, than their higher corticosterone counterparts. Results suggest the existence of INPs in birds, comparable to mammalian LEWIS/FISCHER profiles, where basal corticosterone also underlies responses of comparable variables associated to the phenotypes. Concluding, INP may not be a mammalian distinct feature, leading to discuss whether these profiles represent a parallel phenomenon evolved in birds and mammals, or a common feature inherited from a reptilian ancestor millions of years ago.
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Affiliation(s)
- F. Nicolas Nazar
- Biological and Technological Investigations Institute (IIByT), National Scientific and Technical Research Council (CONICET) and National University of Cordoba, Cordoba, Argentina
| | - Bibiana E. Barrios
- Clinical Biochemistry and Immunology Research Center (CIBICI), National Scientific and Technical Research Council (CONICET) and National University of Cordoba, Cordoba, Argentina
| | - Pete Kaiser
- The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, Scotland, United Kingdom
| | - Raul H. Marin
- Biological and Technological Investigations Institute (IIByT), National Scientific and Technical Research Council (CONICET) and National University of Cordoba, Cordoba, Argentina
| | - Silvia G. Correa
- Clinical Biochemistry and Immunology Research Center (CIBICI), National Scientific and Technical Research Council (CONICET) and National University of Cordoba, Cordoba, Argentina
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Alamino VA, Mascanfroni ID, Montesinos MM, Gigena N, Donadio AC, Blidner AG, Milotich SI, Cheng SY, Masini-Repiso AM, Rabinovich GA, Pellizas CG. Antitumor Responses Stimulated by Dendritic Cells Are Improved by Triiodothyronine Binding to the Thyroid Hormone Receptor β. Cancer Res 2015; 75:1265-74. [PMID: 25672979 DOI: 10.1158/0008-5472.can-14-1875] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Accepted: 01/20/2015] [Indexed: 01/22/2023]
Abstract
Bidirectional cross-talk between the neuroendocrine and immune systems orchestrates immune responses in both physiologic and pathologic settings. In this study, we provide in vivo evidence of a critical role for the thyroid hormone triiodothyronine (T3) in controlling the maturation and antitumor functions of dendritic cells (DC). We used a thyroid hormone receptor (TR) β mutant mouse (TRβPV) to establish the relevance of the T3-TRβ system in vivo. In this model, TRβ signaling endowed DCs with the ability to stimulate antigen-specific cytotoxic T-cell responses during tumor development. T3 binding to TRβ increased DC viability and augmented DC migration to lymph nodes. Moreover, T3 stimulated the ability of DCs to cross-present antigens and to stimulate cytotoxic T-cell responses. In a B16-OVA mouse model of melanoma, vaccination with T3-stimulated DCs inhibited tumor growth and prolonged host survival, in part by promoting the generation of IFNγ-producing CD8(+) T cells. Overall, our results establish an adjuvant effect of T3-TRβ signaling in DCs, suggesting an immediately translatable method to empower DC vaccination approaches for cancer immunotherapy.
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Affiliation(s)
- Vanina A Alamino
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Dpto. Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina
| | - Iván D Mascanfroni
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Dpto. Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina
| | - María M Montesinos
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Dpto. Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina
| | - Nicolás Gigena
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Dpto. Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina
| | - Ana C Donadio
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Dpto. Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina
| | - Ada G Blidner
- Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME-CONICET) and Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Sonia I Milotich
- Hospital Materno-Neonatal Ramón Carrillo, Sanatorio Allende, Córdoba, Argentina
| | - Sheue-Yann Cheng
- Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Ana M Masini-Repiso
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Dpto. Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina
| | - Gabriel A Rabinovich
- Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME-CONICET) and Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Claudia G Pellizas
- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Dpto. Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
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Abstract
Despite decades of research aimed at identifying the causes of postpartum depression (PPD), PPD remains common, and the causes are poorly understood. Many have attributed the onset of PPD to the rapid perinatal change in reproductive hormones. Although a number of human and nonhuman animal studies support the role of reproductive hormones in PPD, several studies have failed to detect an association between hormone concentrations and PPD. The purpose of this review is to examine the hypothesis that fluctuations in reproductive hormone levels during pregnancy and the postpartum period trigger PPD in susceptible women. We discuss and integrate the literature on animal models of PPD and human studies of reproductive hormones and PPD. We also discuss alternative biological models of PPD to demonstrate the potential for multiple PPD phenotypes and to describe the complex interplay of changing reproductive hormones and alterations in thyroid function, immune function, hypothalamic-pituitary-adrenal (HPA) axis function, lactogenic hormones, and genetic expression that may contribute to affective dysfunction. There are 3 primary lines of inquiry that have addressed the role of reproductive hormones in PPD: nonhuman animal studies, correlational studies of postpartum hormone levels and mood symptoms, and hormone manipulation studies. Reproductive hormones influence virtually every biological system implicated in PPD, and a subgroup of women seem to be particularly sensitive to the effects of perinatal changes in hormone levels. We propose that these women constitute a "hormone-sensitive" PPD phenotype, which should be studied independent of other PPD phenotypes to identify underlying pathophysiology and develop novel treatment targets.
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Alvarez TA, Gray PB. Effects of Acute Change in Health Status on Human Female Sexuality. ACTA ACUST UNITED AC 2015. [DOI: 10.4303/jem/235850] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Lee SWH, Liong ML, Yuen KH, Krieger JN. Acupuncture and immune function in chronic prostatitis/chronic pelvic pain syndrome: a randomized, controlled study. Complement Ther Med 2014; 22:965-9. [PMID: 25453515 DOI: 10.1016/j.ctim.2014.10.010] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2014] [Revised: 08/25/2014] [Accepted: 10/10/2014] [Indexed: 11/30/2022] Open
Abstract
OBJECTIVE The immune system has been implicated as one mechanism underlying the benefits of acupuncture therapy. Evidence suggests that acupuncture can ameliorate symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but the association between clinical response and the immune system has not been investigated. DESIGN/SETTING We investigated 12 CP/CPPS patients participating in a prospective randomized clinical trial comparing acupuncture versus sham acupuncture for effects on cellular immunity. Blood samples were taken before the first needling and after the last of 20 treatment sessions (week 10). Patients also completed questionnaires examining their CP/CPPS symptoms and mood status at the baseline and end of study visits. RESULTS At the end of study 8 of 12 participants (67%) were classified as treatment responders, four participants each from the acupuncture and sham groups. The acupuncture group averaged a 5% increase in natural killer cell levels compared to corresponding sham (-13%; p=0.03). Similarly, patients randomized to acupuncture reported a reduction in other white blood cell parameters examined, supporting the possibility that immunity might be important in the pathophysiology of CP/CPPS. CONCLUSIONS The specific effect of acupuncture on CP/CPPS remains unclear. Further research is warranted to examine the mechanisms by which acupuncture therapy may improve clinical symptoms in patients with CP/CPPS. TRIAL REGISTRATION ClinicalTrials.gov number, NCT00260637).
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Affiliation(s)
- Shaun Wen Huey Lee
- School of Pharmacy, Monash University Malaysia, Subang Jaya, Selangor, Malaysia
| | - Men Long Liong
- Department of Urology, Island Hospital, George Town, Penang, Malaysia
| | - Kah Hay Yuen
- School of Pharmaceutical Sciences, Universiti Sains Malaysia, George Town, Penang, Malaysia
| | - John N Krieger
- Department of Urological Surgery, University of Washington, Seattle, 98108 WA, USA.
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Bronson SL, Bale TL. Prenatal stress-induced increases in placental inflammation and offspring hyperactivity are male-specific and ameliorated by maternal antiinflammatory treatment. Endocrinology 2014; 155:2635-46. [PMID: 24797632 PMCID: PMC4060181 DOI: 10.1210/en.2014-1040] [Citation(s) in RCA: 224] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Adverse experiences during gestation such as maternal stress and infection are known risk factors for neurodevelopmental disorders, including schizophrenia, autism, and attention deficit/hyperactivity disorder. The mechanisms by which these distinct exposures may confer similar psychiatric vulnerability remain unclear, although likely involve pathways common to both stress and immune responses at the maternal-fetal interface. We hypothesized that maternal stress-induced activation of immune pathways within the placenta, the sex-specific maternal-fetal intermediary, may contribute to prenatal stress programming effects on the offspring. Therefore, we assessed for markers indicative of stress-induced placental inflammation, and examined the ability of maternal nonsteroidal antiinflammatory drug (NSAID) treatment to ameliorate placental effects and thereby rescue the stress-dysregulation phenotype observed in our established mouse model of early prenatal stress (EPS). As expected, placental gene expression analyses revealed increased levels of immune response genes, including the proinflammatory cytokines IL-6 and IL-1β, specifically in male placentas. NSAID treatment partially ameliorated these EPS effects. Similarly, in adult offspring, males displayed stress-induced locomotor hyperactivity, a hallmark of dopaminergic dysregulation, which was ameliorated by maternal NSAID treatment. Fitting with these outcomes and supportive of dopamine pathway involvement, expression of dopamine D1 and D2 receptors was altered by EPS in males. These studies support an important interaction between maternal stress and a proinflammatory state in the long-term programming effects of maternal stress.
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MESH Headings
- Animals
- Anti-Inflammatory Agents, Non-Steroidal/immunology
- Anti-Inflammatory Agents, Non-Steroidal/pharmacology
- Blotting, Western
- Brain/drug effects
- Brain/immunology
- Brain/metabolism
- Female
- Gene Expression/drug effects
- Gene Expression/immunology
- Humans
- Interleukin-1beta/genetics
- Interleukin-1beta/immunology
- Interleukin-6/genetics
- Interleukin-6/immunology
- Male
- Maze Learning/drug effects
- Mice
- Mice, Inbred C57BL
- Motor Activity/drug effects
- Motor Activity/immunology
- Placenta/drug effects
- Placenta/immunology
- Placenta/metabolism
- Pregnancy
- Prenatal Exposure Delayed Effects/immunology
- Prenatal Exposure Delayed Effects/psychology
- Receptors, Dopamine D1/genetics
- Receptors, Dopamine D1/immunology
- Receptors, Dopamine D2/genetics
- Receptors, Dopamine D2/immunology
- Reverse Transcriptase Polymerase Chain Reaction
- Sex Factors
- Stress, Psychological/immunology
- Stress, Psychological/psychology
- Tyrosine 3-Monooxygenase/immunology
- Tyrosine 3-Monooxygenase/metabolism
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Affiliation(s)
- Stefanie L Bronson
- Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania 19104
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Perrotta C, Buldorini M, Assi E, Cazzato D, De Palma C, Clementi E, Cervia D. The thyroid hormone triiodothyronine controls macrophage maturation and functions: protective role during inflammation. THE AMERICAN JOURNAL OF PATHOLOGY 2013; 184:230-47. [PMID: 24215914 DOI: 10.1016/j.ajpath.2013.10.006] [Citation(s) in RCA: 94] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2013] [Revised: 09/17/2013] [Accepted: 10/04/2013] [Indexed: 12/17/2022]
Abstract
The endocrine system participates in regulating macrophage maturation, although little is known about the modulating role of the thyroid hormones. In vitro results demonstrate a negative role of one such hormone, triiodothyronine (T3), in triggering the differentiation of bone marrow-derived monocytes into unpolarized macrophages. T3-induced macrophages displayed a classically activated (M1) signature. A T3-induced M1-priming effect was also observed on polarized macrophages because T3 reverses alternatively activated (M2) activation, whereas it enhances that of M1 cells. In vivo, circulating T3 increased the content of the resident macrophages in the peritoneal cavity, whereas it reduced the content of the recruited monocyte-derived cells. Of interest, T3 significantly protected mice against endotoxemia induced by lipopolysaccharide i.p. injection; in these damaged animals, decreased T3 levels increased the recruited (potentially damaging) cells, whereas restoring T3 levels decreased recruited and increased resident (potentially beneficial) cells. These data suggest that the anti-inflammatory effect of T3 is coupled to the modulation of peritoneal macrophage content, in a context not fully explained by the M1/M2 framework. Thyroid hormone receptor expression analysis and the use of different thyroid hormone receptor antagonists suggest thyroid hormone receptor β1 as the major player mediating T3 effects on macrophages. The novel homeostatic link between thyroid hormones and the pathophysiological role of macrophages opens new perspectives on the interactions between the endocrine and immune systems.
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Affiliation(s)
- Cristiana Perrotta
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, National Research Council Institute of Neuroscience, Luigi Sacco University Hospital, University of Milan, Milan, Italy
| | | | - Emma Assi
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, National Research Council Institute of Neuroscience, Luigi Sacco University Hospital, University of Milan, Milan, Italy
| | | | - Clara De Palma
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, National Research Council Institute of Neuroscience, Luigi Sacco University Hospital, University of Milan, Milan, Italy
| | - Emilio Clementi
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, National Research Council Institute of Neuroscience, Luigi Sacco University Hospital, University of Milan, Milan, Italy; E. Medea Scientific Institute, Bosisio Parini, Italy.
| | - Davide Cervia
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences, National Research Council Institute of Neuroscience, Luigi Sacco University Hospital, University of Milan, Milan, Italy; Department for Innovation in Biological, Agro-Food and Forest Systems, University of Tuscia, Viterbo, Italy.
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Hafner LM, Cunningham K, Beagley KW. Ovarian steroid hormones: effects on immune responses and Chlamydia trachomatis infections of the female genital tract. Mucosal Immunol 2013; 6:859-75. [PMID: 23860476 DOI: 10.1038/mi.2013.46] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2011] [Accepted: 06/04/2013] [Indexed: 02/04/2023]
Abstract
Female sex hormones are known to regulate the adaptive and innate immune functions of the female reproductive tract. This review aims to update our current knowledge of the effects of the sex hormones estradiol and progesterone in the female reproductive tract on innate immunity, antigen presentation, specific immune responses, antibody secretion, genital tract infections caused by Chlamydia trachomatis, and vaccine-induced immunity.
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Affiliation(s)
- L M Hafner
- Infectious Diseases Program, Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Kelvin Grove, Queensland, Australia.
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A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome. BMC Immunol 2013; 14:29. [PMID: 23800166 PMCID: PMC3698072 DOI: 10.1186/1471-2172-14-29] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2012] [Accepted: 06/11/2013] [Indexed: 11/19/2022] Open
Abstract
Background Though potentially linked to the basic physiology of stress response we still have no clear understanding of Gulf War Illness (GWI), a debilitating condition presenting complex immune, endocrine and neurological symptoms. Here we compared male (n = 20) and female (n = 10) veterans with GWI separately against their healthy counterparts (n = 21 male, n = 9 female) as well as subjects with chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME) (n = 12 male, n = 10 female). Methods Subjects were assessed using a Graded eXercise Test (GXT) with blood drawn prior to exercise, at peak effort (VO2 max) and 4-hours post exercise. Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70), 13, 15, 17 and 23, IFNγ, TNFα and TNFβ in plasma samples from each phase of exercise. Linear classification models were constructed using stepwise variable selection to identify cytokine co-expression patterns characteristic of each subject group. Results Classification accuracies in excess of 80% were obtained using between 2 and 5 cytokine markers. Common to both GWI and CFS, IL-10 and IL-23 expression contributed in an illness and time-dependent manner, accompanied in male subjects by NK and Th1 markers IL-12, IL-15, IL-2 and IFNγ. In female GWI and CFS subjects IL-10 was again identified as a delineator but this time in the context of IL-17 and Th2 markers IL-4 and IL-5. Exercise response also differed between sexes: male GWI subjects presented characteristic cytokine signatures at rest but not at peak effort whereas the opposite was true for female subjects. Conclusions Though individual markers varied, results collectively supported involvement of the IL-23/Th17/IL-17 axis in the delineation of GWI and CFS in a sex-specific way.
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Chereshnev VA, Bocharov G, Bazhan S, Bachmetyev B, Gainova I, Likhoshvai V, Argilaguet JM, Martinez JP, Rump JA, Mothe B, Brander C, Meyerhans A. Pathogenesis and treatment of HIV infection: the cellular, the immune system and the neuroendocrine systems perspective. Int Rev Immunol 2013; 32:282-306. [PMID: 23617796 DOI: 10.3109/08830185.2013.779375] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Infections with HIV represent a great challenge for the development of strategies for an effective cure. The spectrum of diseases associated with HIV ranges from opportunistic infections and cancers to systemic physiological disorders like encephalopathy and neurocognitive impairment. A major progress in controlling HIV infection has been achieved by highly active antiretroviral therapy (HAART). However, HAART does neither eliminate the virus reservoirs in form of latently infected cells nor does it completely reconstitute immune reactivity and physiological status. Furthermore, the failure of the STEP vaccine trial and the only marginal efficacies of the RV144 trial together suggest that the causal relationships between the complex sets of viral and immunological processes that contribute to protection or disease pathogenesis are still poorly understood. Here, we provide an up-to-date overview of HIV-host interactions at the cellular, the immune system and the neuroendocrine systems level. Only by integrating this multi-level knowledge one will be able to handle the systems complexity and develop new methodologies of analysis and prediction for a functional restoration of the immune system and the health of the infected host.
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Affiliation(s)
- V A Chereshnev
- Institute of Immunology and Physiology, Ural Branch RAS, Ekaterinburg, Russia.
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Lara LJ, Rostagno MH. Impact of Heat Stress on Poultry Production. Animals (Basel) 2013; 3:356-69. [PMID: 26487407 PMCID: PMC4494392 DOI: 10.3390/ani3020356] [Citation(s) in RCA: 643] [Impact Index Per Article: 53.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Revised: 04/05/2013] [Accepted: 04/22/2013] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Due to the common occurrence of environmental stressors worldwide, many studies have investigated the detrimental effects of heat stress on poultry production. It has been shown that heat stress negatively affects the welfare and productivity of broilers and laying hens. However, further research is still needed to improve the knowledge of basic mechanisms associated to the negative effects of heat stress in poultry, as well as to develop effective interventions. Abstract Understanding and controlling environmental conditions is crucial to successful poultry production and welfare. Heat stress is one of the most important environmental stressors challenging poultry production worldwide. The detrimental effects of heat stress on broilers and laying hens range from reduced growth and egg production to decreased poultry and egg quality and safety. Moreover, the negative impact of heat stress on poultry welfare has recently attracted increasing public awareness and concern. Much information has been published on the effects of heat stress on productivity and immune response in poultry. However, our knowledge of basic mechanisms associated to the reported effects, as well as related to poultry behavior and welfare under heat stress conditions is in fact scarce. Intervention strategies to deal with heat stress conditions have been the focus of many published studies. Nevertheless, effectiveness of most of the interventions has been variable or inconsistent. This review focuses on the scientific evidence available on the importance and impact of heat stress in poultry production, with emphasis on broilers and laying hens.
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Affiliation(s)
- Lucas J Lara
- Department of Animal Sciences, Purdue University, 915 West State Street, West Lafayette, IN 47907, USA.
| | - Marcos H Rostagno
- Livestock Behavior Research Unit, USDA-ARS, 125 South Russell Street, West Lafayette, IN 47907, USA.
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Avitsur R, Maayan R, Weizman A. Neonatal stress modulates sickness behavior: role for proinflammatory cytokines. J Neuroimmunol 2013; 257:59-66. [PMID: 23489747 DOI: 10.1016/j.jneuroim.2013.02.009] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2012] [Revised: 01/22/2013] [Accepted: 02/14/2013] [Indexed: 11/30/2022]
Abstract
Neonatal stress increased the duration and augmented symptoms of sickness behavior induced by influenza virus infection or endotoxin challenge in mice. Since proinflammatory cytokines were implicated in sickness behavior, the present study sought to determine the effect of neonatal stress on cytokines-induced sickness behavior and on proinflammatory cytokine secretion. Data indicate that separation of mouse pups from the dams at an early age (maternal separation, MSP) increased the duration and augmented some of the symptoms of sickness behavior induced by proinflammatory cytokines. In addition, MSP partially suppressed cytokine and corticosterone secretion in response to endotoxin administration. These data may suggest that MSP increased sensitivity to the effects of proinflammatory cytokines on sickness behavior following an immune challenge.
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Affiliation(s)
- Ronit Avitsur
- School of Behavioral Sciences, The Academic College of Tel Aviv-Yaffo, Yaffo, Israel.
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Effects of feeding Bt maize to sows during gestation and lactation on maternal and offspring immunity and fate of transgenic material. PLoS One 2012; 7:e47851. [PMID: 23091650 PMCID: PMC3473024 DOI: 10.1371/journal.pone.0047851] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2012] [Accepted: 09/21/2012] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND We aimed to determine the effect of feeding transgenic maize to sows during gestation and lactation on maternal and offspring immunity and to assess the fate of transgenic material. METHODOLOGY/PRINCIPAL FINDINGS On the day of insemination, sows were assigned to one of two treatments (n = 12/treatment); 1) non-Bt control maize diet or 2) Bt-MON810 maize diet, which were fed for ~143 days throughout gestation and lactation. Immune function was assessed by leukocyte phenotyping, haematology and Cry1Ab-specific antibody presence in blood on days 0, 28 and 110 of gestation and at the end of lactation. Peripheral-blood mononuclear cell cytokine production was investigated on days 28 and 110 of gestation. Haematological analysis was performed on offspring at birth (n = 12/treatment). Presence of the cry1Ab transgene was assessed in sows' blood and faeces on day 110 of gestation and in blood and tissues of offspring at birth. Cry1Ab protein presence was assessed in sows' blood during gestation and lactation and in tissues of offspring at birth. Blood monocyte count and percentage were higher (P<0.05), while granulocyte percentage was lower (P<0.05) in Bt maize-fed sows on day 110 of gestation. Leukocyte count and granulocyte count and percentage were lower (P<0.05), while lymphocyte percentage was higher (P<0.05) in offspring of Bt maize-fed sows. Bt maize-fed sows had a lower percentage of monocytes on day 28 of lactation and of CD4(+)CD8(+) lymphocytes on day 110 of gestation, day 28 of lactation and overall (P<0.05). Cytokine production was similar between treatments. Transgenic material or Cry1Ab-specific antibodies were not detected in sows or offspring. CONCLUSIONS/SIGNIFICANCE Treatment differences observed following feeding of Bt maize to sows did not indicate inflammation or allergy and are unlikely to be of major importance. These results provide additional data for Bt maize safety assessment.
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Dhabhar FS, Malarkey WB, Neri E, McEwen BS. Stress-induced redistribution of immune cells--from barracks to boulevards to battlefields: a tale of three hormones--Curt Richter Award winner. Psychoneuroendocrinology 2012; 37:1345-68. [PMID: 22727761 PMCID: PMC3412918 DOI: 10.1016/j.psyneuen.2012.05.008] [Citation(s) in RCA: 368] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2011] [Revised: 05/14/2012] [Accepted: 05/16/2012] [Indexed: 01/13/2023]
Abstract
BACKGROUND The surveillance and effector functions of the immune system are critically dependent on the appropriate distribution of immune cells in the body. An acute or short-term stress response induces a rapid and significant redistribution of immune cells among different body compartments. Stress-induced leukocyte redistribution may be a fundamental survival response that directs leukocyte subpopulations to specific target organs during stress, and significantly enhances the speed, efficacy and regulation of an immune response. Immune responses are generally enhanced in compartments (e.g., skin) that are enriched with leukocytes, and suppressed in compartments that are depleted of leukocytes during/following stress. The experiments described here were designed to elucidate the: (1) Time-course, trajectory, and subpopulation-specificity of stress-induced mobilization and trafficking of blood leukocytes. (2) Individual and combined actions of the principal stress hormones, norepinephrine (NE), epinephrine (EPI), and corticosterone (CORT), in mediating mobilization or trafficking of specific leukocyte subpopulations. (3) Effects of stress/stress hormones on adhesion molecule, L-selectin (CD62L), expression by each subpopulation to assess its adhesion/functional/maturation status. METHODS Male Sprague Dawley rats were stressed (short-term restraint, 2-120 min), or adrenalectomized and injected with vehicle (VEH), NE, EPI, CORT, or their combinations, and blood was collected for measurement of hormones and flow cytometric quantification of leukocyte subpopulations. RESULTS Acute stress induced an early increase/mobilization of neutrophils, lymphocytes, helper T cells (Th), cytolytic T cells (CTL), and B cells into the blood, followed by a decrease/trafficking of all cell types out of the blood, except neutrophil numbers that continued to increase. CD62L expression was increased on neutrophils, decreased on Th, CTL, and natural killer (NK) cells, and showed a biphasic decrease on monocytes & B cells, suggesting that CD62L is involved in mediating the redistribution effects of stress. Additionally, we observed significant differences in the direction, magnitude, and subpopulation specificity of the effects of each hormone: NE increased leukocyte numbers, most notably CD62L⁻/⁺ neutrophils and CD62L⁻ B cells. EPI increased monocyte and neutrophil numbers, most notably CD62L⁻/⁺ neutrophils and CD62L⁻ monocytes, but decreased lymphocyte numbers with CD62L⁻/⁺ CTL and CD62L⁺ B cells being especially sensitive. CORT decreased monocyte, lymphocyte, Th, CTL, and B cell numbers with CD62L⁻ and CD62L⁺ cells being equally affected. Thus, naïve (CD62L⁺) vs. memory (CD62L⁻) T cells, classical (CD62L⁺) vs. non-classical (CD62L⁻) monocytes, and similarly distinct functional subsets of other leukocyte populations are differentially mobilized into the blood and trafficked to tissues by stress hormones. CONCLUSION Stress hormones orchestrate a large-scale redistribution of immune cells in the body. NE and EPI mobilize immune cells into the bloodstream, and EPI and CORT induce traffic out of the blood possibly to tissue surveillance pathways, lymphoid tissues, and sites of ongoing or de novo immune activation. Immune cell subpopulations appear to show differential sensitivities and redistribution responses to each hormone depending on the type of leukocyte (neutrophil, monocyte or lymphocyte) and its maturation/functional characteristics (e.g., non-classical/resident or classical/inflammatory monocyte, naïve or central/effector memory T cell). Thus, stress hormones could be administered simultaneously or sequentially to induce specific leukocyte subpopulations to be mobilized into the blood, or to traffic from blood to tissues. Stress- or stress hormone-mediated changes in immune cell distribution could be clinically harnessed to: (1) Direct leukocytes to sites of vaccination, wound healing, infection, or cancer and thereby enhance protective immunity. (2) Reduce leukocyte traffic to sites of inflammatory/autoimmune reactions. (3) Sequester immune cells in relatively protected compartments to minimize exposure to cytotoxic treatments like radiation or localized chemotherapy. (4) Measure biological resistance/sensitivity to stress hormones in vivo. In keeping with the guidelines for Richter Award manuscripts, in addition to original data we also present a model and synthesis of findings in the context of the literature on the effects of short-term stress on immune cell distribution and function.
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Affiliation(s)
- Firdaus S Dhabhar
- Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305-5135, USA.
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