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Zuluaga P, Teniente-Serra A, Fuster D, Quirant-Sánchez B, Hernandez-Rubio A, Martínez-Cáceres E, Muga R. Increased Natural Killer Cells Are Associated with Alcohol Liver Fibrosis and with T Cell and Cytotoxic Subpopulations Change. J Clin Med 2022; 11:jcm11020305. [PMID: 35054000 PMCID: PMC8780875 DOI: 10.3390/jcm11020305] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 12/31/2021] [Indexed: 12/20/2022] Open
Abstract
Natural killer (NK) cells play a therapeutic role in liver fibrosis (LF). We aimed to analyze NK cells in heavy drinkers without cirrhosis or decompensated liver disease and establish correlations with other related subpopulations. Data on sociodemographic characteristics, alcohol consumption, laboratory parameters, and immunophenotyping of NK (CD16+/CD56+), T (CD3+), B (CD19+), NKT (CD16+/CD56+/CD3+), and cytotoxic (CD3-CD8+) cells were collected. Fibrosis-4 (FIB-4) scores were used to compare patients without (FIB-4 < 1.45) and with (FIB-4 > 3.25) advanced LF (ALF). We included 136 patients (76% male) with a mean age of 49 years who had a 15-year alcohol use disorder (AUD) and alcohol consumption of 164 g/day. Patients with ALF (n = 25) presented significantly lower absolute total lymphocyte, T cell, B cell, and NKT cell numbers than patients without LF (n = 50; p < 0.01). However, the NK cells count was similar (208 ± 109 cells/µL vs. 170 ± 105 cells/µL) in both groups. The T cells percentage was lower (80.3 ± 5.6% vs. 77 ± 7%; p = 0.03) and the NK cells percentage was higher (9.7 ± 5% vs. 13 ± 6%; p = 0.02) in patients with ALF than in those without LF. The percentages of NK cells and T cells were inversely correlated in patients without (r = –0.65, p < 0.01) and with ALF (r = −0.64; p < 0.01). Additionally, the NK cells and CD3-CD8+ cell percentages were positively correlated in patients without (r = 0.87, p < 0.01) and with (r = 0.92; p < 0.01) ALF. Conclusions: Heavy drinkers without decompensated liver disease showed an increase in NK cells related to T cells lymphopenia and an increase in cytotoxic populations. The interaction of NK cells with other subpopulations may modify alcohol-related liver disease progression.
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Affiliation(s)
- Paola Zuluaga
- Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol-IGTP, Universitat Autònoma de Barcelona, 08916 Barcelona, Spain; (D.F.); (A.H.-R.); (R.M.)
- Correspondence:
| | - Aina Teniente-Serra
- Department of Immunology, Hospital Universitari Germans Trias i Pujol-IGTP, Universitat Autònoma de Barcelona, 08916 Barcelona, Spain; (A.T.-S.); (B.Q.-S.); (E.M.-C.)
| | - Daniel Fuster
- Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol-IGTP, Universitat Autònoma de Barcelona, 08916 Barcelona, Spain; (D.F.); (A.H.-R.); (R.M.)
| | - Bibiana Quirant-Sánchez
- Department of Immunology, Hospital Universitari Germans Trias i Pujol-IGTP, Universitat Autònoma de Barcelona, 08916 Barcelona, Spain; (A.T.-S.); (B.Q.-S.); (E.M.-C.)
| | - Anna Hernandez-Rubio
- Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol-IGTP, Universitat Autònoma de Barcelona, 08916 Barcelona, Spain; (D.F.); (A.H.-R.); (R.M.)
| | - Eva Martínez-Cáceres
- Department of Immunology, Hospital Universitari Germans Trias i Pujol-IGTP, Universitat Autònoma de Barcelona, 08916 Barcelona, Spain; (A.T.-S.); (B.Q.-S.); (E.M.-C.)
| | - Roberto Muga
- Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol-IGTP, Universitat Autònoma de Barcelona, 08916 Barcelona, Spain; (D.F.); (A.H.-R.); (R.M.)
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Hoare J, Fouche JP, Phillips N, Heany SJ, Myer L, Zar HJ, Stein DJ. Alcohol use is associated with mental health problems and brain structural alterations in adolescents with perinatally acquired HIV infection on ART. Alcohol 2021; 97:59-66. [PMID: 34536544 DOI: 10.1016/j.alcohol.2021.09.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 09/09/2021] [Accepted: 09/09/2021] [Indexed: 10/20/2022]
Abstract
Alcohol use, presents unique challenges for HIV-1 treatment in adolescents with perinatally acquired infection. The effects of alcohol on host-virus interaction in the brain and the immune system remains understudied in this population. Adolescents with perinatally acquired HIV infection (PHIV) well established on ART, from the Cape Town Adolescent Antiretroviral Cohort who self-reported alcohol use (PHIV + alcohol) (n = 26) were compared to age matched 26 PHIV (PHIV-alcohol) and 26 healthy controls (HC) who reported no use of alcohol. Participants completed clinical investigations including highly-sensitive CRP (hs-CRP), a comprehensive neurocognitive test battery and mental health measures. In addition, we investigated the relationship between alcohol use in PHIV and diffusion tensor imaging (DTI) and structural brain magnetic resonance imaging (MRI) to determine fractional anisotropy (FA), mean diffusivity (MD), grey and white matter volumes and cortical thickness. PHIV (mean age 12,5 years; mean age of ART initiation 3.15 years) reported an occasional weekend drinking pattern of alcohol use. hs-CRP was significantly different between groups, with PHIV + alcohol higher than PHIV-alcohol and HC. General intelligence, attention, working memory, processing speed and executive function were more impaired in the PHIV + alcohol than PHIV alone, with HC having the highest scores. In addition, self-concept was significantly lower in PHIV + alcohol. The Child Behavior Checklist (CBCL) Externalizing behaviour, internalising behaviour and CBCL Total problems were significantly higher in PHIV + alcohol. FA of the superior corona radiata, superior fronto-occipital fasciculus and corpus callosum was significantly lower in PHIV + alcohol compared to PHIV-alcohol and MD of the corona radiata was significantly increased in PHIV + alcohol. The cortical thickness of the lateral orbitofrontal, middle frontal and precentral gyri were significantly lower in PHIV + alcohol compared to PHIV-alcohol and HC. In conclusion PHIV associated impairments in systemic inflammation, cognitive function, mental health and changes in brain structure may be exacerbated by alcohol use, even if only occasional use. However, the study is cross-sectional, which is not able to distinguish between cause and effect.
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Pérez-García A, Arroyo-Valerio AG, Bustos-Esquivel MA, Quispe-Siccha RM, Zaldívar-Fujigaki JL, Pacheco-Yepez J, Kershenobich D, López-Alvarenga JC, Hernández-Ruiz J. Young adult binge drinkers have immunophenotypical disarrangements in peripheral natural killer cells. Alcohol 2019; 81:70-78. [PMID: 31265902 DOI: 10.1016/j.alcohol.2019.06.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 06/17/2019] [Accepted: 06/19/2019] [Indexed: 11/18/2022]
Abstract
Alcohol consumption is an issue of worldwide relevance and a problem of national scale in Mexico. The consumption pattern of large amounts of alcohol on the weekends is rapidly increasing in young adults between 18 and 29 years. Despite various studies that have focused on the noxious effect of alcohol in immunity, the changes in the immunoprofiles of peripheral blood cells have not been completely described. Natural killer cells (NKCs) are lymphoid-origin cells of the immune system that are responsible for defense against tumors, among other functions. In homeostatic conditions, they are found to be in a state of "dynamic balance" between activation and inhibition stimuli, which, if broken, may lead to immunosuppression or activation of cytotoxic mechanisms. In this study, we evaluated the immunoprofile of peripheral NKCs of 54 young adults, 29 of whom were binge drinkers and 25 of whom were low risk (LR), as classified by validated tools. Drinking habits were assessed. Blood samples were collected to perform hematic biometry and liver enzyme tests. Peripheral NKCs were identified by FACS, and stained for CCR2, CCR4, CCR5, CXCR4, CD69, CD127, CD137, TLR4, and Granzyme B. The data were analyzed using the t test and Mann-Whitney's U test for contrasts, and the effect size was obtained in order to evaluate the impact of each immunoprofile. The binge group showed increased expression of CCR5 and PD-1 in NKCs, respective to the LR group, and decreased expression of TLR4, along with fewer CCR4+ cells. Moreover, the increase found in CCR5 and PD-1 expression was correlated with the number of drinks in the last drinking session. Our findings show that young binge drinkers have different immunoprofiles that could suggest an early status of immunosuppression and trafficking of NKCs to the liver, which could be related to the onset of early liver damage, early in a subject's lifespan.
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Affiliation(s)
- Adolfo Pérez-García
- Experimental Surgery Service, Hospital General de México "Dr. Eduardo Liceaga", Dr. Balmis 148 Colonia Doctores, Delegación, Cuauhtémoc, 06726 CDMX, Mexico
| | - América Guadalupe Arroyo-Valerio
- Research Department, Hospital General de México "Dr. Eduardo Liceaga", Dr. Balmis 148 Colonia Doctores, Delegación Cuauhtémoc, 06726 CDMX, Mexico
| | - Mayra A Bustos-Esquivel
- Research & Technological Development Unit (UIDT) UNAM-HGM, Dr. Balmis 148 Colonia, Doctores, Delegación Cuauhtémoc, 06726 CDMX, Mexico
| | - Rosa M Quispe-Siccha
- Research Department, Hospital General de México "Dr. Eduardo Liceaga", Dr. Balmis 148 Colonia Doctores, Delegación Cuauhtémoc, 06726 CDMX, Mexico; Research & Technological Development Unit (UIDT) UNAM-HGM, Dr. Balmis 148 Colonia, Doctores, Delegación Cuauhtémoc, 06726 CDMX, Mexico
| | - José Luis Zaldívar-Fujigaki
- Clinical Research, Centro Médico Nacional "20 de Noviembre", ISSSTE, Félix Cuevas 540, Col del Valle Sur, Delegación Benito Juárez, 03100 CDMX, Mexico
| | - Judith Pacheco-Yepez
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Calle Salvador Díaz Mirón S/N, Santo Tomás, Alcaldia Miguel Hidalgo, 11340 CDMX, Mexico
| | - David Kershenobich
- National Institute of Medical Sciences and Nutrition, "Salvador Zubirán,", Avenida Vasco de Quiroga No. 15, Colonia Belisario Domínguez Sección XVI, Delegación Tlalpan, CDMX 14080, Mexico
| | - J C López-Alvarenga
- Department of Human Genetics, School of Medicine, University of Texas, Rio Grande Valley, Texas, United States; Research Division Mexican-American University of the North (UMAN), Reynosa, Tamaulipas, Mexico
| | - Joselín Hernández-Ruiz
- Clinical Pharmacology Unit, Hospital General de México "Dr. Eduardo Liceaga", Dr. Balmis 148 Colonia Doctores, Alcaldia Cuauhtémoc, 06726 CDMX, Mexico.
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Zuluaga P, Sanvisens A, Martínez-Cáceres E, Teniente A, Tor J, Muga R. Over-expression of CD8 + T-cell activation is associated with decreased CD4 + cells in patients seeking treatment of Alcohol Use Disorder. Drug Alcohol Depend 2017; 180:7-13. [PMID: 28850904 DOI: 10.1016/j.drugalcdep.2017.07.023] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2017] [Revised: 06/13/2017] [Accepted: 07/21/2017] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Harmful alcohol consumption may have an impact on the adaptive immune system through an imbalance in T cell subpopulations and changes in cell activation. We aimed to analyze profiles of CD4 and CD8T cell activation in patients with alcohol use disorder (AUD). METHODS We used a cross-sectional study with patients seeking treatment of the disorder. Blood samples for immunophenotyping were obtained at admission. Profiles of T cell activation were defined: (I) CD38+/HLA-DR+, (II) CD38+/HLA-DR-, (III) CD38-/HLA-DR+, (IV) CD38-/HLA-DR- and compared with healthy controls. We calculated a CD8+ T cell activation indicator (AI) that was defined as the quotient of non-activated cells (CD38-/HLA-DR-) and activated cells (CD38+/HLA-DR+). RESULTS 60 patients were eligible (83%M); median age was 49 years [IQR: 44-54] and alcohol consumption was 145g/day [IQR: 90-205]. Mean±SD of CD38+/HLA-DR- was 50.3±50.6 cells/μL in patients and 33.5±24.5 cells/μL in controls (p=0.03), for the CD38-/HLA-DR+ it was 61±62.2 cells/μL in patients and 21.2±17.3 cells/μL in controls (p<0.001) and for the CD38+/HLA-DR+ it was 20.2±15.6 cells/μL in patients and 10.8±10.3 cells/μL in controls (p<0.001). In patients, an inverse correlation was observed between absolute number and percentage of CD4+ T cells, and the percentage of CD38+/HLA-DR+CD8+ T cells (r=0.37, p=0.003; r=0.2, p=0.086, respectively). CONCLUSIONS Patients with AUD have an increased expression of immune activation with respect to healthy individuals. This excess of activated CD8+ T cells correlates with the absolute CD4+ T cells.
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Affiliation(s)
- Paola Zuluaga
- Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain
| | - Arantza Sanvisens
- Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain
| | - Eva Martínez-Cáceres
- Department of Immunology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain
| | - Aina Teniente
- Department of Immunology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain
| | - Jordi Tor
- Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain
| | - Robert Muga
- Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916, Badalona, Spain.
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Pérez-García A, Arroyo-Valerio AG, Zaldivar-Fujigaki JL, Bustos-Esquivel MA, Gastelum-Strozzi A, Padilla-Castañeda MA, Reding-Bernal A, Kershenobich D, Hernández-Ruiz J. Young adult binge drinkers have immunophenotypic changes in peripheral polymorphonuclear cells and monocytes. THE AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE 2017; 44:403-412. [DOI: 10.1080/00952990.2017.1316985] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Adolfo Pérez-García
- Laboratory of Liver, Pancreas and Motility, Experimental Medicine Unit, National Autonomous University of Mexico (UNAM) at General Hospital of Mexico “Dr. Eduardo Liceaga,” Mexico City, Mexico
- Experimental Surgery Service, General Hospital of Mexico “Dr. Eduardo Liceaga,” Mexico City, Mexico
| | | | - José Luis Zaldivar-Fujigaki
- Laboratory of Liver, Pancreas and Motility, Experimental Medicine Unit, National Autonomous University of Mexico (UNAM) at General Hospital of Mexico “Dr. Eduardo Liceaga,” Mexico City, Mexico
| | | | - Alfonso Gastelum-Strozzi
- Research and Technical Development Unit (CCADET UNAM) at General Hospital of Mexico “Dr. Eduardo Liceaga,” Mexico City, Mexico
| | - Miguel A. Padilla-Castañeda
- Research and Technical Development Unit (CCADET UNAM) at General Hospital of Mexico “Dr. Eduardo Liceaga,” Mexico City, Mexico
| | - Arturo Reding-Bernal
- Research Department, General Hospital of Mexico “Dr. Eduardo Liceaga,” Mexico City, Mexico
| | - David Kershenobich
- National Institute of Medical Sciences and Nutrition, “Salvador Zubirán,” Mexico City, Mexico
| | - Joselín Hernández-Ruiz
- Laboratory of Liver, Pancreas and Motility, Experimental Medicine Unit, National Autonomous University of Mexico (UNAM) at General Hospital of Mexico “Dr. Eduardo Liceaga,” Mexico City, Mexico
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Zuluaga P, Sanvisens A, Teniente A, Fuster D, Tor J, Martínez-Cáceres E, Muga R. Wide array of T-cell subpopulation alterations in patients with alcohol use disorders. Drug Alcohol Depend 2016; 162:124-9. [PMID: 27038675 DOI: 10.1016/j.drugalcdep.2016.02.046] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Revised: 02/12/2016] [Accepted: 02/27/2016] [Indexed: 12/20/2022]
Abstract
BACKGROUND Alcohol abuse impacts innate and adaptive immunity and predisposes to infections. However, prevalence and correlations of cellular immune alterations in large case series is underreported. We aimed to analyze quantitative alterations of T-lymphocyte subpopulations in patients with alcohol use disorder (AUD). METHODS cross-sectional study in patients admitted for detoxification between January 1, 2002 and December 31, 2012. Socio-demographic and alcohol use characteristics and blood samples for biochemistry, hematology and immune phenotype was obtained at admission. RESULTS 238 patients (79.8%M) were eligible; age at admission was 43 years (interquartile range [IQR]: 38-51 years), the amount of alcohol consumption was 180 g/day (IQR: 120-200 g/day) and median duration of AUD was 18 years (IQR: 9-25 years). Compared to healthy individuals, 50% of patients had significantly fewer double-negative (DN) T-lymphocytes (<34 × 10(9)/L) and 23% had more double-positive (DP) T-cells (>52 × 10(9)/L). In addition, 24% of patients had high number of CD8(+) cells (>735 × 10(9)/L) and 13% had low CD4(+) cell counts (<600 × 10(9)/L). In multivariable analysis, age, sex, serum albumin, and current cocaine use were predictors of T-cell subpopulation alterations. Women were three-times (OR=3.5, 95%CI:1.3-9.5) more likely to present with higher DP T-lymphocytes than men. CONCLUSIONS Quantitative alterations of T-cell subpopulations are frequent in patients seeking treatment of AUD. Assessment of cellular immunity in this population may help to identify those at increased risk of immune alterations.
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Affiliation(s)
- Paola Zuluaga
- Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
| | - Arantza Sanvisens
- Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
| | - Aina Teniente
- Department of Immunology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
| | - Daniel Fuster
- Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
| | - Jordi Tor
- Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
| | - Eva Martínez-Cáceres
- Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
| | - Roberto Muga
- Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
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Gacouin A, Roussel M, Le Priol J, Azzaoui I, Uhel F, Fest T, Le Tulzo Y, Tadie JM. Acute alcohol exposure has an independent impact on C-reactive protein levels, neutrophil CD64 expression, and subsets of circulating white blood cells differentiated by flow cytometry in nontrauma patients. Shock 2015; 42:192-8. [PMID: 24827394 DOI: 10.1097/shk.0000000000000195] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Acute and massive alcohol exposure (blood alcohol concentration of ≥1 g/L) is a common way to consume alcohol. In a prospective study performed in critically ill nontrauma patients, we compared C-reactive protein (CRP) values, circulating subsets of white blood cells, and neutrophil CD64 indexes recorded at admission to the intensive care unit between abstinent or moderate drinkers (n = 173), patients with acute or chronic alcohol exposure (n = 32), and patients with acute exposure but not chronically exposed to alcohol (n = 27). Values for CRP (P < 0.001), circulating neutrophils (P < 0.001), and neutrophil CD64 indexes (P < 0.001) were significantly lower in patients acutely exposed compared with the other patients, whereas values for B lymphocytes (P < 0.001) and cytotoxic (P < 0.001) and noncytotoxic T lymphocytes (P < 0.001) were significantly higher. After multiple regression analysis, alcohol exposure remained independently associated with values of CRP, neutrophils CD4 indexes, cytotoxic and noncytotoxic T lymphocytes, and CD16-negative and -positive monocytes. These results were not affected by the presence or absence of infection at admission. Our results suggest that in nontrauma critically ill patients, acute alcohol exposure diminishes inflammation and increases numbers of circulating B and T lymphocytes.
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Affiliation(s)
- Arnaud Gacouin
- *CHU Rennes, Maladies Infectieuses et Réanimation Médicale; †Inserm-CIC; ‡Univ Rennes 1, Faculté de Médecine, Biosit; §CHU Rennes, Laboratoire d'Hématologie; and ∥Inserm U 917, Rennes, France
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González-Reimers E, Santolaria-Fernández F, Martín-González MC, Fernández-Rodríguez CM, Quintero-Platt G. Alcoholism: A systemic proinflammatory condition. World J Gastroenterol 2014; 20:14660-14671. [PMID: 25356029 PMCID: PMC4209532 DOI: 10.3748/wjg.v20.i40.14660] [Citation(s) in RCA: 125] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Excessive ethanol consumption affects virtually any organ, both by indirect and direct mechanisms. Considerable research in the last two decades has widened the knowledge about the paramount importance of proinflammatory cytokines and oxidative damage in the pathogenesis of many of the systemic manifestations of alcoholism. These cytokines derive primarily from activated Kupffer cells exposed to Gram-negative intestinal bacteria, which reach the liver in supra-physiological amounts due to ethanol-mediated increased gut permeability. Reactive oxygen species (ROS) that enhance the inflammatory response are generated both by activation of Kupffer cells and by the direct metabolic effects of ethanol. The effects of this increased cytokine secretion and ROS generation lie far beyond liver damage. In addition to the classic consequences of endotoxemia associated with liver cirrhosis that were described several decades ago, important research in the last ten years has shown that cytokines may also induce damage in remote organs such as brain, bone, muscle, heart, lung, gonads, peripheral nerve, and pancreas. These effects are even seen in alcoholics without significant liver disease. Therefore, alcoholism can be viewed as an inflammatory condition, a concept which opens the possibility of using new therapeutic weapons to treat some of the complications of this devastating and frequent disease. In this review we examine some of the most outstanding consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver.
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Agudelo M, Khatavkar P, Yndart A, Yoo C, Rosenberg R, Devieux JG, Malow RM, Nair M. Alcohol abuse and HIV infection: role of DRD2. Curr HIV Res 2014; 12:234-42. [PMID: 25053368 PMCID: PMC4300295 DOI: 10.2174/1570162x12666140721115045] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2013] [Revised: 04/25/2014] [Accepted: 04/28/2014] [Indexed: 11/22/2022]
Abstract
According to a survey from the HIV Cost and Services Utilization Study (HCSUS), approximately 53% of HIV-infected patients reported drinking alcohol and 8% were classified as heavy drinkers. The role of alcohol as a risk factor for HIV infection has been widely studied and recent research has found a significant association between heavy alcohol consumption and lower levels of CD4 T cells among HIV-infected alcoholics. Although there is evidence on the role of alcohol as a risk factor for HIV transmission and disease progression, there is a need for population studies to determine the genetic mechanisms that affect alcohol's role in HIV disease progression. One of the mechanisms of interest is the dopaminergic system. To date, the effects of dopamine on HIV neuroimmune pathogenesis are not well understood; however, dopaminergic neural degeneration due to HIV is known to occur by viral invasion into the brain via immune cells, and modulation of dopamine in the CNS may be a common mechanism by which different types of substances of abuse impact HIV disease progression. Although previous studies have shown an association of D(2) dopamine receptor (DRD2) polymorphisms with severity of alcohol dependence, the expression of this allele risk on HIV patients with alcohol dependence has not been systematically explored. In the current study, DRD2 Taq1A and C957T SNP genotyping analyses were performed in 165 HIV-infected alcohol abusers and the results were examined with immune status and CD4 counts.
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Affiliation(s)
| | | | | | | | | | | | | | - Madhavan Nair
- Department of Immunology, Institute of NeuroImmune Pharmacology, College of Medicine, AHC-I 308, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA.
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Matos LC, Batista P, Monteiro N, Ribeiro J, Cipriano MA, Henriques P, Girão F, Carvalho A. Lymphocyte subsets in alcoholic liver disease. World J Hepatol 2013; 5:46-55. [PMID: 23646229 PMCID: PMC3642723 DOI: 10.4254/wjh.v5.i2.46] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2012] [Revised: 09/04/2012] [Accepted: 11/14/2012] [Indexed: 02/06/2023] Open
Abstract
AIM To compare lymphocyte subsets between healthy controls and alcoholics with liver disease. METHODS The patient cohort for this study included individuals who were suspected to have alcoholic liver disease (ALD) and who had undergone liver biopsy (for disease grading and staging, doubts about diagnosis, or concurrent liver disease; n = 56). Normal controls included patients who were admitted for elective cholecystectomy due to non-complicated gallstones (n = 27). Formalin-fixed, paraffin-embedded liver biopsy specimens were sectioned and stained with hematoxylin and eosin and Perls' Prussian blue. The non-alcoholic steatohepatitis score was used to assess markers of ALD. Lymphocyte population subsets were determined by flow cytometry. T lymphocytes were identified (CD3(+)), and then further subdivided into CD4(+) or CD8(+) populations. B lymphocytes (CD19(+)) and natural killer (NK) cell numbers were also measured. In addition to assessing lymphocyte subpopulation differences between ALD patients and controls, we also compared subsets of alcoholic patients without cirrhosis or abstinent cirrhotic patients to normal controls. RESULTS The patient cohort primarily consisted of older men. Active alcoholism was present in 66.1%. Reported average daily alcohol intake was 164.9 g and the average lifetime cumulative intake was 2211.6 kg. Cirrhosis was present in 39.3% of the patients and 66.1% had significant fibrosis (perisinusoidal and portal/periportal fibrosis, bridging fibrosis, or cirrhosis) in their liver samples. The average Mayo end-stage liver disease score was 7.6. No hereditary hemochromatosis genotypes were found. ALD patients (n = 56) presented with significant lymphopenia (1.5 × 10(9)/L ± 0.5 × 10(9)/L vs 2.1 × 10(9)/L ± 0.5 × 10(9)/L, P < 0.0001), due to a decrease in all lymphocyte subpopulations, except for NK lymphocytes: CD3(+) (1013.0 ± 406.2/mm(3) vs 1523.0 ± 364.6/mm(3), P < 0.0001), CD4(+) (713.5 ± 284.7/mm(3) vs 992.4 ± 274.7/mm(3), P < 0.0001), CD8(+) (262.3 ± 140.4/mm(3) vs 478.9 ± 164.6/mm(3), P < 0.0001), and CD19(+) (120.6 ± 76.1/mm(3) vs 264.6 ± 88.0/mm(3), P < 0.0001). CD8(+) lymphocytes suffered the greatest reduction, as evidenced by an increase in the CD4(+)/CD8(+) ratio (3.1 ± 1.3 vs 2.3 ± 0.9, P = 0.013). This ratio was associated with the stage of fibrosis on liver biopsy (r s = 0.342, P = 0.01) and with Child-Pugh score (r s = 0.482, P = 0.02). The number of CD8(+) lymphocytes also had a positive association with serum ferritin levels (r s = 0.345, P = 0.009). Considering only patients with active alcoholism but not cirrhosis (n = 27), we found similar reductions in total lymphocyte counts (1.8 × 10(9)/L ± 0.3 × 10(9)/L vs 2.1 × 10(9)/L ± 0.5 × 10(9)/L, P = 0.018), and in populations of CD3(+) (1164.7 ± 376.6/mm(3) vs 1523.0 ± 364.6/mm(3), P = 0.001), CD4(+) (759.8 ± 265.0/mm(3) vs 992.4 ± 274.7/mm(3), P = 0.003), CD8(+) (330.9 ± 156.3/mm(3) vs 478.9 ± 164.6/mm(3), P = 0.002), and CD19(+) (108.8 ± 64.2/mm(3) vs 264.6 ± 88.0/mm(3), P < 0.0001). In these patients, the CD4(+)/CD8(+) ratio and the number of NK lymphocytes was not significantly different, compared to controls. Comparing patients with liver cirrhosis but without active alcohol consumption (n = 11), we also found significant lymphopenia (1.3 × 10(9)/L ± 0.6 × 10(9)/L vs 2.1 × 10(9)/L ± 0.5 × 10(9)/L, P < 0.0001) and decreases in populations of CD3(+) (945.5 ± 547.4/mm(3) vs 1523.0 ± 364.6/mm(3), P = 0.003), CD4(+) (745.2 ± 389.0/mm(3) vs 992.4 ± 274.7/mm(3), P = 0.032), CD8(+) (233.9 ± 120.0/mm(3) vs 478.9 ± 164.6/mm(3), P < 0.0001), and CD19(+) (150.8 ± 76.1/mm(3) vs 264.6 ± 88.0/mm(3), P = 0.001). The NK lymphocyte count was not significantly different, but, in this group, there was a significant increase in the CD4(+)/CD8(+) ratio (3.5 ± 1.3 vs 2.3 ± 0.9, P = 0.01). CONCLUSION All patient subsets presented with decreased lymphocyte counts, but only patients with advanced fibrosis presented with a significant increase in the CD4(+)/CD8(+) ratio.
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Affiliation(s)
- Luís Costa Matos
- Luís Costa Matos, Armando Carvalho, Faculty of Medicine of the University of Coimbra, 3004-504 Coimbra, Portugal
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Current world literature. Curr Opin Pediatr 2012; 24:277-84. [PMID: 22414891 DOI: 10.1097/mop.0b013e328351e459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Zhang HM, Nie JS, Li X, Niu Q. Characteristic analysis of peripheral blood mononuclear cell apoptosis in coke oven workers. J Occup Health 2011; 54:44-50. [PMID: 22186298 DOI: 10.1539/joh.11-0155-oa] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVES The aim of the present study was to determine the peripheral blood mononuclear cell (PBMC) apoptosis in coke oven workers so that we can take effective measures to protect coke oven workers. METHODS The subjects, 129 coke oven workers and 37 warehouse workers (controls), were investigated using a questionnaire to collect information about their age, working years, smoking and drinking habits, vocational history and other general information. The coke oven workers were divided into the oven-bottom group (34), oven-side group (48) and oven-top group (47) according to their working sites and environmental monitoring data. The concentration of benzo[a]pyrene (B[a]P) and the subjects' urinary 1-hydroxypyrene (1-OH-Py) levels were determined by HPLC. Additionally, the PBMCs were separated from blood samples, and the early and late apoptosis rates were determined by flow cytometry. RESULTS The airborne B[a]P concentrations were 19.5 ± 13.2, 185.9 ± 38.6 and 1,623.5 ± 435.8 ng/m(3) at the bottom, side and top of the oven, respectively, and were higher than in the controls' workplaces 10.2 ± 7.6 ng/m(3). Urinary 1-OH-Py, indicating the B[a]P's internal exposure level, was significantly higher in the exposed groups than in the controls (p<0.05). Compared with the controls, the coke oven workers' PBMC apoptosis rates were significantly increased and increased in association with the B[a]P level. PBMC apoptosis increased in association with the 1-OH-Py level and coking operation years and decreased in association with years of alcohol consumption. CONCLUSIONS PBMC apoptosis in the coke oven workers was associated with the 1-OH-Py level, coke operation years and years of alcohol consumption and may be induced by B[a]P.
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Affiliation(s)
- Hong Mei Zhang
- Department of Occupational and Environmental Health, Shanxi Medical University
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Hahn JA, Woolf-King SE, Muyindike W. Adding fuel to the fire: alcohol's effect on the HIV epidemic in Sub-Saharan Africa. Curr HIV/AIDS Rep 2011; 8:172-80. [PMID: 21713433 DOI: 10.1007/s11904-011-0088-2] [Citation(s) in RCA: 106] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Alcohol consumption adds fuel to the HIV epidemic in sub-Saharan Africa (SSA). SSA has the highest prevalence of HIV infection and heavy episodic drinking in the world. Alcohol consumption is associated with behaviors such as unprotected sex and poor medication adherence, and biological factors such as increased susceptibility to infection, comorbid conditions, and infectiousness, which may synergistically increase HIV acquisition and onward transmission. Few interventions to decrease alcohol consumption and alcohol-related sexual risk behaviors have been developed or implemented in SSA, and few HIV or health policies or services in SSA address alcohol consumption. Structural interventions, such as regulating the availability, price, and advertising of alcohol, are challenging to implement due to the preponderance of homemade alcohol and beverage industry resistance. This article reviews the current knowledge on how alcohol impacts the HIV epidemic in SSA, summarizes current interventions and policies, and identifies areas for increased research and development.
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Affiliation(s)
- Judith A Hahn
- Department of Medicine, University of California, San Francisco, USA.
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