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Ng KTP, Pang L, Wang JQ, She WH, Tsang SHY, Lo CM, Man K, Cheung TT. Indications of pro-inflammatory cytokines in laparoscopic and open liver resection for early-stage hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2024; 23:257-264. [PMID: 37903711 DOI: 10.1016/j.hbpd.2023.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 10/06/2023] [Indexed: 11/01/2023]
Abstract
BACKGROUND Our clinical practice of laparoscopic liver resection (LLR) had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma (HCC) over open liver resection (OLR), but the underlying mechanisms are not clear. This study was to find out whether systemic inflammation plays an important role. METHODS A total of 103 patients with early-stage HCC under liver resection were enrolled (LLR group, n = 53; OLR group, n = 50). The expression of 9 inflammatory cytokines in patients at preoperation, postoperative day 1 (POD1) and POD7 was quantified by Luminex Multiplex assay. The relationships of the cytokines and the postoperative outcomes were compared between LLR and OLR. RESULTS Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative levels. Compared to OLR, the POD1 levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1) in the LLR group were significantly lower. Higher POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during operation. The levels of these cytokines were positively associated with postoperative liver injury, and the length of hospital stay. Importantly, a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver resection. CONCLUSIONS Significantly lower level of GM-CSF, IL-6, IL-8, and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.
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Affiliation(s)
- Kevin Tak-Pan Ng
- Department of Surgery, HKU-SZH & School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Li Pang
- Department of Surgery, HKU-SZH & School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Jia-Qi Wang
- Department of Surgery, HKU-SZH & School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Wong Hoi She
- Department of Surgery, HKU-SZH & School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Simon Hing-Yin Tsang
- Department of Surgery, HKU-SZH & School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Chung Mau Lo
- Department of Surgery, HKU-SZH & School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Kwan Man
- Department of Surgery, HKU-SZH & School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Tan To Cheung
- Department of Surgery, HKU-SZH & School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China.
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Potocnik I, Kerin-Povsic M, Markovic-Bozic J. The influence of anaesthesia on cancer growth. Radiol Oncol 2024; 58:9-14. [PMID: 38378027 PMCID: PMC10878770 DOI: 10.2478/raon-2024-0012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Accepted: 11/22/2023] [Indexed: 02/22/2024] Open
Abstract
BACKGROUND Oncological patients make up a large proportion of all surgical patients. Through its influence on the patient's inflammatory and immune system, the choice of anaesthetic technique has an indirect impact on the health of the individual patient and on public health. Both the specific and the non-specific immune system have a major influence on the recurrence of carcinomas. The pathophysiological basis for growth and metastasis after surgery is the physiological response to stress. Inflammation is the organism's universal response to stress. Anaesthetics and adjuvants influence perioperative inflammation in different ways and have an indirect effect on tumour growth and metastasis. In vitro studies have shown how individual anaesthetics influence the growth and spread of cancer, but clinical studies have not confirmed these results. Nevertheless, it is advisable to use an anaesthetic that has shown lesser effect on the growth of cancer cells in vitro. CONCLUSIONS In this review, we focus on the area of the effects of anaesthesia on tumour growth. The field is still relatively unexplored, there are only few clinical prospective studies and their results are controversial. Based on the review of new research findings we report on recommendations about anaesthetics and anaesthetic techniques that might be preferable for oncological surgical procedures.
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Affiliation(s)
- Iztok Potocnik
- Department of Anaesthesiology and Intensive Care, Institute of Oncology Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Milena Kerin-Povsic
- Department of Anaesthesiology and Intensive Care, Institute of Oncology Ljubljana, Ljubljana, Slovenia
| | - Jasmina Markovic-Bozic
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Department of Anaesthesiology and Surgical Intensive Therapy, University Medical Centre Ljubljana, Ljubljana, Slovenia
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Hai HH, Aw P, Teng TZJ, Shelat VG. Perioperative steroid administration reduces overall complications in patients undergoing liver resection: A meta-analysis. World J Gastrointest Surg 2021; 13:1079-1094. [PMID: 34621482 PMCID: PMC8462075 DOI: 10.4240/wjgs.v13.i9.1079] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 04/03/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatic resection (HR) results in an inflammatory response that can be modified by perioperative steroid administration. However, it remains to be determined if this response's attenuation translates to a reduction in complications. AIM To evaluate if perioperative administration of steroids reduces complications following HR. METHODS A systematic review of randomized controlled trials (RCTs) was conducted on PubMed, Embase, and Cochrane Central Register of Controlled Trials to evaluate the effect of perioperative steroid (compared to placebo or no intervention) use in patients undergoing HR. Clinical outcomes were extracted, and meta-analysis was performed. RESULTS 8 RCTs including 590 patients were included. Perioperative steroid administration was associated with significant reduction in postoperative complications [odds ratios: 0.58; 95% confidence intervals (CI): 0.35-0.97, P = 0.04]. There was also improvement in biochemical and inflammatory markers, including serum bilirubin on postoperative day 1 [MD: -0.27; 95%CI: (-0.47, -0.06), P = 0.01], C-reactive protein on postoperative day 3 [MD: -4.89; 95%CI: (-5.83, -3.95), P < 0.001], and interleukin-6 on postoperative day 1 [MD: -54.84; 95%CI: (-63.91, -45.76), P < 0.001]. CONCLUSION Perioperative steroids administration in HR may reduce overall complications, postoperative bilirubin, and inflammation. Further studies are needed to determine the optimal dose and duration and patient selection.
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Affiliation(s)
- Hao-Han Hai
- NUS Yong Loo Lin School of Medicine, Singapore 119228, Singapore
| | - Phoebe Aw
- NUS Yong Loo Lin School of Medicine, Singapore 119228, Singapore
| | | | - Vishal G Shelat
- NTU Lee Kong Chian School of Medicine, Singapore 308232, Singapore
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
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Zak A, Siwinska N, Elzinga S, Barker VD, Stefaniak T, Schanbacher BJ, Place NJ, Niedzwiedz A, Adams AA. Effects of advanced age and pituitary pars intermedia dysfunction on components of the acute phase reaction in horses. Domest Anim Endocrinol 2020; 72:106476. [PMID: 32380311 DOI: 10.1016/j.domaniend.2020.106476] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 02/12/2020] [Accepted: 03/01/2020] [Indexed: 11/24/2022]
Abstract
Age, neurodegenerative disorders, and dysfunction of insulin secretion may be correlated with increased systemic concentrations of acute phase markers. Thus, the study aimed to determine the effect of age, pituitary pars intermedia dysfunction (PPID), and insulin dysregulation (ID) associated with PPID, on markers of the acute phase reaction. Twenty-nine mix-breed horses of both sexes were classified into groups: (1) healthy adult controls, (2) healthy non-PPID geriatric horses, (3) PPID ID+ horses, and (4) PPID ID- horses. Whole blood proinflammatory cytokine gene expression and serum concentrations of pro- and anti-inflammatory cytokines and acute phase proteins were measured. The data were analyzed using the Mann-Whitney U-test, and correlations between groups of data were assessed using Spearman's correlation coefficient. The tests were statistically significant if P < 0.05. No differences in the whole blood cytokine gene expression, serum cytokine concentrations, or acute phase proteins were noted between the groups. In the PPID ID group, there was a strong correlation between the ACTH concentration after the administration of thyrotropin-releasing hormone and the expression of IL-8 (r = 0.941; P = 0.0321). In the PPID ID+ group, there was a strong correlation between basal insulin concentrations and serum amyloid A (SAA; r = 0.936; P = 0.0083) as well as between postprandial insulin concentrations and SAA (r = 0.965; P = 0.001). These data suggest that neurodegeneration in horses moderately affects circulating markers of inflammation and that ID in horses with PPID influences acute phase inflammatory markers.
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Affiliation(s)
- A Zak
- Department of Internal Diseases with Clinic for Horses, Dogs and Cats, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.
| | - N Siwinska
- Department of Internal Diseases with Clinic for Horses, Dogs and Cats, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland
| | - S Elzinga
- Department of Veterinary Science, MH Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546, USA
| | - V D Barker
- Department of Veterinary Science, MH Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546, USA
| | - T Stefaniak
- Department of Immunology, Pathophysiology and Veterinary Preventive Medicine, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland
| | - B J Schanbacher
- Department of Population Medicine & Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
| | - N J Place
- Department of Population Medicine & Diagnostic Sciences, Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
| | - A Niedzwiedz
- Department of Internal Diseases with Clinic for Horses, Dogs and Cats, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland
| | - A A Adams
- Department of Veterinary Science, MH Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546, USA
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Yang L, Zhang Z, Kong J, Wang W. Systematic Review and Meta-Analysis of the Benefit and Safety of Preoperative Administration of Steroid in Patients Undergoing Liver Resection. Front Pharmacol 2019; 10:1442. [PMID: 31849683 PMCID: PMC6894012 DOI: 10.3389/fphar.2019.01442] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Accepted: 11/12/2019] [Indexed: 02/05/2023] Open
Abstract
Objective: To evaluate the benefit and safety of preoperative administration of steroid in patients undergoing liver resection. Methods: Randomized controlled trials (RCTs) which comparing preoperative administration of steroid in patients undergoing liver resection with control group were identified through a systematic literature search in PubMed, Embase, and Cochrane Library Central databases. This meta-analysis was carried out to assess the liver function, inflammatory response, and postoperative complications after liver surgery. Results: Six RCTs including 411 patients were reviewed. The pooled result showed that there was no significant difference in the incidence of overall complications between the steroid group and the control group (OR, 0.57; 95% CI, 0.27–1.17; P = 0.13). With respect to specific complications, no significant difference was detected between the two groups in infection complications (OR, 0.95; 95% CI, 0.13–6.95; P = 0.96), wound complications (OR, 0.65; 95% CI, 0.32–1.33; P = 0.24), liver failure (OR, 0.41; 95% CI, 0.10–1.64; P = 0.21), bile leakage (OR, 0.57; 95% CI, 0.17–1.89; P = 0.36), and pleural effusion (OR, 1.24; 95% CI, 0.55–2.78; P = 0.60). For liver function, the level of serum total bilirubin (TB) on postoperative day 1 (POD 1) was significantly decreased associated with the intervention of steroid (MD, −0.54; 95% CI, −0.94 to −0.15; P = 0.007). However, no significant difference was found in the level of alanine aminotransferase (ALT) (MD, −69.39; 95% CI, −226.52 to 87.75; P = 0.39) and aspartate aminotransferase (AST) (MD, −93.44; 95% CI, −275.68 to 88.80; P = 0.31) on POD 1 between the two groups. Serum IL-6 level on POD 1 (MD, −57.98; 95% CI, −73.04 to −42.91; P < 0.00001) and CRP level on POD 3 (MD, −4.83; 95% CI, −6.07 to −3.59; P < 0.00001) were significantly reduced in the steroid group comparing to the control group. Compared with the control group, the level of early postoperative IL-10 was significant higher in the steroid group (MD, 17.89; 95% CI, 3.89 to 31.89; P = 0.01). Conclusion: Preoperative administration of steroid in liver resection can promote the recovery of liver function and inhibit the inflammatory response without increasing postoperative complications. Further studies should focus on determining which patients would benefit most from the steroid.
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Affiliation(s)
- Lingpeng Yang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
| | - Zifei Zhang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China.,Department of General Surgery, The Affiliated Hospital of Xizang Minzu University, Xianyang, China
| | - Junjie Kong
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
| | - Wentao Wang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China
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6
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Correia CR, Gaifem J, Oliveira MB, Silvestre R, Mano JF. The influence of surface modified poly(l-lactic acid) films on the differentiation of human monocytes into macrophages. Biomater Sci 2018; 5:551-560. [PMID: 28128374 DOI: 10.1039/c6bm00920d] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Macrophages play a crucial role in the biological performance of biomaterials, as key factors in defining the optimal inflammation-healing balance towards tissue regeneration and implant integration. Here, we investigate how different surface modifications performed on poly(l-lactic acid) (PLLA) films would influence the differentiation of human monocytes into macrophages. We tested PLLA films without modification, surface-modified by plasma treatment (pPLLA) or by combining plasma treatment with different coating materials, namely poly(l-lysine) and a series of proteins from the extracellular matrix: collagen I, fibronectin, vitronectin, laminin and albumin. While all the tested films are non-cytotoxic, differences in cell adhesion and morphology are observed. Monocyte-derived macrophages (MDM) present a more rounded shape in non-modified films, while a more elongated phenotype is observed containing filopodia-like and podosome-like structures in all modified films. No major differences are found for the expression of HLA-DR+/CD80+ and CD206+/CD163+ surface markers, as well as for the ability of MDM to phagocytize. Interestingly, MDM differentiated on pPLLA present the highest expression of MMP9. Upon differentiation, MDM in all surface modified films present lower amounts of IL-6 and IL-10 compared to non-modified films. After stimulating MDM with the potent pro-inflammatory agent LPS, pPLLA and poly(l-lysine) and fibronectin-modified films reveal a significant reduction in IL-6 secretion, while the opposite effect is observed with IL-10. Of note, in comparison to non-modified films, all surface modified films induce a significant reduction of the IL-6/IL-10 ratio, a valuable prognosticator of the pro- versus anti-inflammatory balance. These findings provide important insights into MDM-biomaterial interactions, while strengthening the need for designing immune-informed biomaterials.
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Affiliation(s)
- Clara R Correia
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4805-017 Barco, Guimarães, Portugal. and ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
| | - Joana Gaifem
- ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. and Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal
| | - Mariana B Oliveira
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4805-017 Barco, Guimarães, Portugal. and ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
| | - Ricardo Silvestre
- ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. and Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal
| | - João F Mano
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4805-017 Barco, Guimarães, Portugal. and ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
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Ashtary-Larky D, Lamuchi-Deli N, Milajerdi A, Bakhtiar Salehi M, Alipour M, Kooti W, Ashtary-Larky P, Alamiri F, Sheikhi A, Afrisham R. Inflammatory and Biochemical Biomarkers in Response to High Intensity Resistance Training in Trained and Untrained Men. Asian J Sports Med 2017; In Press. [DOI: 10.5812/asjsm.13739] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/17/2025] Open
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8
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Ghafourian M, Ashtary-Larky D, Chinipardaz R, Eskandary N, Mehavaran M. Inflammatory Biomarkers' Response to Two Different Intensities of a Single Bout Exercise Among Soccer Players. IRANIAN RED CRESCENT MEDICAL JOURNAL 2016; 18:e21498. [PMID: 27175304 PMCID: PMC4862257 DOI: 10.5812/ircmj.21498] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/19/2014] [Revised: 10/10/2014] [Accepted: 10/28/2014] [Indexed: 11/16/2022]
Abstract
Background: There is a strong relationship between physical inactivity and low-grade inflammation and its adverse health outcomes, particularly cardiovascular disease. The level of anti-inflammatory and pro-inflammatory cytokines may be changed by exercise. Objectives: The aim of the present study was to determine the response of certain inflammatory biomarkers to exercise with differences in maximal oxygen consumption (VO2max). These biomarkers were IL-1β, TNF-α, hs-CRP, IL-6, sICAM-1, IL-10, and ratios of TNF-α/IL-10 and IL-6/IL-in circulating peripheral blood (PB). Materials and Methods: In a semi-experimental study, twenty male students who performed regular football exercise at least three days a week, for two years, were selected by easy sampling at Shahid Chamran university of Iran. Subjects were then randomly assigned to two groups: the protocol of the first group was 30 minutes of running at a speed of 65% of VO2max, and the second group performed six periodic repetitions with three minutes at a speed of 85% of VO2max with a 90-second rest between the repetitions. Blood samples were taken at baseline, immediately after the exercise and at rest. Cytokine levels were quantified by the Sandwich enzyme-linked immunosorbent assay (ELISA) method. Results: The first protocol resulted in a decrease of serum IL-1β to 3.77 ± 0.28 pg/mL at rest, from 4.33 ± 0.28 at baseline and 4.32 ± 0.34 immediately after exercise (P = 0.008 and P = 0.013, respectively). There was also a decrease in the level of sICAM-1 to 260.11±15.64 ng/mL at rest, from 329.58 ± 20.82 at baseline and 302.7 ± 20.49 post exercise (P = 0.013 and P = 0.038, respectively). On the other hand, IL-6 and ratio of IL-6/IL-10 increased to 6.55±0.84 pg/mL and 2.12 ± 0.37 immediately after exercise from baseline (2.73 ± 0.58 and 1.16 ± 0.33) and rest (2.49 ± 0.45 and 0.95 ± 0.19) in the second protocol (P = 0.001 and P = 0.001, respectively for IL-6, and P = 0.047 and P = 0.024, respectively for IL-6/IL-10). Conclusions: The data of the present study demonstrated that a single bout of exercise with higher-intensity induces a transient increase in some proinflammatory markers, and lower-intensity can reduce these biomarkers.
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Affiliation(s)
- Mehri Ghafourian
- Department of Immunology, Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Damoon Ashtary-Larky
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
- Department of Biochemistry, Faculty of Medicine, Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
- Corresponding Author: Damoon Ashtary-Larky, Department of Biochemistry, Faculty of Medicine, Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran. Tel: +98-9366113574, Fax: +98-611333203, E-mail:
| | - Rahim Chinipardaz
- Department of Statistics, Faculty of Mathematics and Computer Sciences, Shahid Chamran University, Ahvaz, IR Iran
| | - Nahid Eskandary
- Department of Immunology, Faculty of Medicine, Esfahan University of Medical Sciences, Esfahan, IR Iran
| | - Mousa Mehavaran
- Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Shahid Chamran University, Ahvaz, IR Iran
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Crenn P, Neveux N, Chevret S, Jaffray P, Cynober L, Melchior JC, Annane D. Plasma l-citrulline concentrations and its relationship with inflammation at the onset of septic shock: A pilot study. J Crit Care 2014; 29:315.e1-315.e6. [DOI: 10.1016/j.jcrc.2013.11.015] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2013] [Revised: 11/12/2013] [Accepted: 11/18/2013] [Indexed: 11/27/2022]
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10
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Richardson AJ, Laurence JM, Lam VWT. Use of pre-operative steroids in liver resection: a systematic review and meta-analysis. HPB (Oxford) 2014; 16:12-9. [PMID: 23461716 PMCID: PMC3892310 DOI: 10.1111/hpb.12066] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2012] [Accepted: 12/05/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND By attenuating the systemic inflammatory response to major surgery, the pre-operative administration of steroids may reduce the incidence of complications. METHODS A systematic review was conducted to identify randomized controlled trials (RCT) comparing pre-operative steroid administration with placebo during a liver resection. Meta-analyses were performed. RESULTS Five RCTs were identified including a total of 379 patients. Pre-operative steroids were associated with statistically significant reductions in the levels of serum bilirubin and interleukin 6 (IL-6) on post-operative day one. There was a trend towards a lower incidence of post-operative complications and prothrombin time (PT), but this did not reach statistical significance. CONCLUSION Pre-operative steroids may be associated with a clinically significant benefit in liver resection.
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Affiliation(s)
- Arthur J Richardson
- Department of Surgery, Westmead Hospital, Sydney, NSW, Australia; Discipline of Surgery, University of Sydney, Sydney, NSW, Australia
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An agent-based model of cellular dynamics and circadian variability in human endotoxemia. PLoS One 2013; 8:e55550. [PMID: 23383223 PMCID: PMC3559552 DOI: 10.1371/journal.pone.0055550] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2012] [Accepted: 12/30/2012] [Indexed: 01/01/2023] Open
Abstract
As cellular variability and circadian rhythmicity play critical roles in immune and inflammatory responses, we present in this study an agent-based model of human endotoxemia to examine the interplay between circadian controls, cellular variability and stochastic dynamics of inflammatory cytokines. The model is qualitatively validated by its ability to reproduce circadian dynamics of inflammatory mediators and critical inflammatory responses after endotoxin administration in vivo. Novel computational concepts are proposed to characterize the cellular variability and synchronization of inflammatory cytokines in a population of heterogeneous leukocytes. Our results suggest that there is a decrease in cell-to-cell variability of inflammatory cytokines while their synchronization is increased after endotoxin challenge. Model parameters that are responsible for IκB production stimulated by NFκB activation and for the production of anti-inflammatory cytokines have large impacts on system behaviors. Additionally, examining time-dependent systemic responses revealed that the system is least vulnerable to endotoxin in the early morning and most vulnerable around midnight. Although much remains to be explored, proposed computational concepts and the model we have pioneered will provide important insights for future investigations and extensions, especially for single-cell studies to discover how cellular variability contributes to clinical implications.
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12
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The role of Src kinase in macrophage-mediated inflammatory responses. Mediators Inflamm 2012; 2012:512926. [PMID: 23209344 PMCID: PMC3504478 DOI: 10.1155/2012/512926] [Citation(s) in RCA: 223] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2012] [Accepted: 09/28/2012] [Indexed: 12/28/2022] Open
Abstract
Src kinase (Src) is a tyrosine protein kinase that regulates cellular metabolism, survival, and proliferation. Many studies have shown that Src plays multiple roles in macrophage-mediated innate immunity, such as phagocytosis, the production of inflammatory cytokines/mediators, and the induction of cellular migration, which strongly implies that Src plays a pivotal role in the functional activation of macrophages. Macrophages are involved in a variety of immune responses and in inflammatory diseases including rheumatoid arthritis, atherosclerosis, diabetes, obesity, cancer, and osteoporosis. Previous studies have suggested roles for Src in macrophage-mediated inflammatory responses; however, recently, new functions for Src have been reported, implying that Src functions in macrophage-mediated inflammatory responses that have not been described. In this paper, we discuss recent studies regarding a number of these newly defined functions of Src in macrophage-mediated inflammatory responses. Moreover, we discuss the feasibility of Src as a target for the development of new pharmaceutical drugs to treat macrophage-mediated inflammatory diseases. We provide insights into recent reports regarding new functions for Src that are related to macrophage-related inflammatory responses and the development of novel Src inhibitors with strong immunosuppressive and anti-inflammatory properties, which could be applied to various macrophage-mediated inflammatory diseases.
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13
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Deng S, Yu K, Zhang B, Yao Y, Liu Y, He H, Zhang H, Cui M, Fu J, Lian Z, Li N. Effects of over-expression of TLR2 in transgenic goats on pathogen clearance and role of up-regulation of lysozyme secretion and infiltration of inflammatory cells. BMC Vet Res 2012; 8:196. [PMID: 23082910 PMCID: PMC3560201 DOI: 10.1186/1746-6148-8-196] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2012] [Accepted: 10/17/2012] [Indexed: 01/07/2023] Open
Abstract
Background Toll-like receptor 2 (TLR2) is important to host recognition of invading gram-positive microbes. In goats, these microbes can cause serious mastitis, anthrax, tetanus, and other problems. Transgenic goats constitutively over-expressing TLR2 in many tissues serve as a suitable model for the study of the role of TLR2 over-expression in bacterial clearance. Results Capra hircus TLR2 over-expression vector (p3S-LoxP-TLR2) was used to generate transgenic goats by egg microinjection. The integration efficiency was 8.57%. Real-time PCR and immunohistochemical results confirmed that the goats over-expressing the TLR2 gene (Tg) expressed more TLR2 than wild-type goats (WT). Monocyte-macrophages from the bloodstreams of transgenic goats were stimulated with synthetic bacterial lipoprotein (Pam3CSK4) and by the promotion of interleukin-6 (IL-6) and IL-10 expression in vitro. The oxidative damage was significantly reduced, and lysozyme (LZM) secretion was found to be up-regulated. Ear tissue samples from transgenic goats that had been stimulated with Pam3CSK4 via hypodermic injection showed that transgenic individuals can undergo the inflammation response very quickly. Conclusions Over-expression of TLR2 was found to decrease radical damage to host cells through low-level production of NO and MDA and to promote the clearance of invasive bacteria by up-regulating lysozyme secretion and filtration of inflammatory cells to the infected site.
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Affiliation(s)
- Shoulong Deng
- National key Lab of Agro-Biotechnology, China Agricultural University, Beijing 100193, People's Republic of China
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14
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Qiu YD, Wang S, Yang Y, Yan XP. Omega-3 polyunsaturated fatty acids promote liver regeneration after 90% hepatectomy in rats. World J Gastroenterol 2012; 18:3288-95. [PMID: 22783054 PMCID: PMC3391767 DOI: 10.3748/wjg.v18.i25.3288] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2011] [Revised: 01/12/2012] [Accepted: 04/10/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the effectiveness of omega-3 polyunsaturated fatty acid (ω-3 PUFA) administration on liver regeneration after 90% partial hepatectomy (PH) in rats.
METHODS: ω-3 PUFAs were intravenously injected in the ω-3 PUFA group before PH surgery. PH, sparing only the caudate lobe, was performed in both the control and the ω-3 PUFA group. Survival rates, liver weight/body weight ratios, liver weights, HE staining, transmission electron microscope imaging, nuclear-associated antigen Ki-67, enzyme-linked immunosorbent assay and signal transduction were evaluated to analyze liver regeneration.
RESULTS: All rats in the control group died within 30 h after hepatectomy. Survival rates in the ω-3 PUFA group were 20/20 at 30 h and 4/20 1 wk after PH. Liver weight/body weight ratios and liver weights increased significantly in the ω-3 PUFA group. The structure of sinusoidal endothelial cells and space of Disse was greatly restored in the ω-3 PUFA group compared to the control group after PH. In the ω-3 PUFA group, interleukin (IL)-4 and IL-10 levels were significantly increased whereas IL-6 and tumor necrosis factor-α levels were dramatically decreased. In addition, activation of protein kinase B (Akt) and of signal transducer and activator of transcription 3 signaling pathway were identified at an earlier time after PH in the ω-3 PUFA group.
CONCLUSION: Omega-3 polyunsaturated fatty acids may prevent acute liver failure and promote liver regeneration after 90% hepatectomy in rats.
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Takiishi T, Tadokoro CE, Rizzo LV, de Moraes LV. Early IL-10 production is essential for syngeneic graft acceptance. J Leukoc Biol 2012; 92:259-64. [PMID: 22416256 DOI: 10.1189/jlb.1111569] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
We performed a comparative study and evaluated cellular infiltrates and anti-inflammatory cytokine production at different time-points after syngeneic or allogeneic skin transplantation. We observed an early IL-10 production in syngeneic grafts compared with allografts. This observation prompted us to investigate the role of IL-10 in isograft acceptance. For this, we used IL-10 KO and WT mice to perform syngeneic transplantation, where IL-10 was absent in the graft or in the recipient. The majority of syngeneic grafts derived from IL-10 KO donors did not engraft or was only partially accepted, whereas IL-10 KO mice transplanted with skin from WT donors accepted the graft. We evaluated IL-10 producers in the transplanted skin and observed that epithelial cells were the major source. Taken together, our data show that production of IL-10 by donor cells, but not by the recipient, is determinant for graft acceptance and strongly suggest that production of this cytokine by keratinocytes immediately upon transplantation is necessary for isograft survival.
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Affiliation(s)
- Tatiana Takiishi
- Laboratory of Clinical Immunology, Department of Immunology, Instituto de Ciências Biomédicas, University of São Paulo, São Paulo, Brazil
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Abstract
Over the years the surgical stress response and the efforts to modify it have been the subject of a great deal of research. Most recently this has led to the development of 'enhanced recovery' programmes which are revolutionizing perioperative patient care across the UK.
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Affiliation(s)
- Leigh Kelliher
- Department of Anaesthesia, Royal Surrey County Hospital NHS Foundation Trust, Guildford GU2 7XX.
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17
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McFarlane D, Wolf RF, McDaniel KA, White GL. Age-associated alteration in innate immune response in captive baboons. J Gerontol A Biol Sci Med Sci 2011; 66:1309-17. [PMID: 21860017 DOI: 10.1093/gerona/glr146] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Baboons are an ideal model for studies of human inflammatory response due to their physiological and immunological similarities to people; however; little is known about how age affects immune function in the baboon. We sought to determine if baboons show age-related innate immune changes similar to that described in people. Age was correlated with increased serum C-reactive protein and interleukin-6 or, however, no change in interleukin-10 concentration was observed (n = 120 baboons). Cytokine release from unstimulated peripheral blood mononuclear cells as well as following immune (lipopolysaccharide) stimulation increased with age. When whole blood was assayed, both lipopolysaccharide stimulated and unstimulated samples showed an age-related increase in interleukin-6 response, although the unstimulated cytokine response was reduced compared with that observed in peripheral blood mononuclear cells. Tumor necrosis factor-α response was not related to age. Cytokine response in lipopolysaccharide-stimulated whole blood was negatively correlated with serum DHEA-S concentration and positively correlated with TGF-β concentration.
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Affiliation(s)
- Dianne McFarlane
- Department of Physiological Sciences, Center of Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA.
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18
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Dello SAWG, Bloemen JG, van de Poll MCG, van Dam RM, Stoot JHMB, van den Broek MAJ, Buurman WA, Bemelmans MHA, Olde Damink SWM, Dejong CHC. Gut and liver handling of interleukin-6 during liver resection in man. HPB (Oxford) 2011; 13:324-31. [PMID: 21492332 PMCID: PMC3093644 DOI: 10.1111/j.1477-2574.2010.00289.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Plasma interleukin-6 (IL-6) levels increase during liver resection. The source of this IL-6 is hitherto unclear. It has been demonstrated that the hepatosplanchnic area takes up IL-6 but the role of the gut and liver is unknown. The aim of the present study was to investigate the role of the gut and liver in IL-6 homeostasis during liver surgery. METHODS Before and after partial hepatectomy, IL-6 was measured in blood sampled from the radial artery, and the hepatic and portal vein. Blood flow was measured to assess IL-6 fluxes (flow times AV-differences) across the gut, liver and hepatosplanchnic area. RESULTS In 22 patients undergoing liver resection, IL-6 release from the gut after transection was 90.9 (30.1) ng/min (P < 0.001), whereas net IL-6 uptake by the liver equalled 83.4 (41.7) ng/min (P < 0.01). Overall hepatosplanchnic flux was 7.3 (43.5) ng/min after transection and did not differ significantly from zero. Overall hepatosplanchnic flux was 87.8 (41.5) ng/min in the major resection group and -59.8 (67.5) ng/min in the minor resection group (P < 0.05). DISCUSSION The gut releases IL-6 and the liver takes up IL-6 before and after liver resection. The loss of IL-6 uptake as a result of a small functional remnant liver could lead to higher IL-6 levels after surgery.
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Affiliation(s)
- Simon AWG Dello
- Department of Surgery, Maastricht University Medical Center & Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht UniversityMaastricht
| | - Johanne G Bloemen
- Department of Surgery, Maastricht University Medical Center & Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht UniversityMaastricht
| | - Marcel CG van de Poll
- Department of Surgery, Maastricht University Medical Center & Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht UniversityMaastricht
| | - Ronald M van Dam
- Department of Surgery, Maastricht University Medical Center & Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht UniversityMaastricht
| | - Jan HMB Stoot
- Department of Surgery, Orbis Medical CenterSittard, the Netherlands
| | - Maartje AJ van den Broek
- Department of Surgery, Maastricht University Medical Center & Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht UniversityMaastricht
| | - Wim A Buurman
- Department of Surgery, Maastricht University Medical Center & Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht UniversityMaastricht
| | - Marc HA Bemelmans
- Department of Surgery, Maastricht University Medical Center & Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht UniversityMaastricht
| | - Steven WM Olde Damink
- Department of Surgery, Maastricht University Medical Center & Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht UniversityMaastricht,Department of Surgery, University College London Hospitals, and University College London, Division of Surgery and Interventional ScienceUK
| | - Cornelis HC Dejong
- Department of Surgery, Maastricht University Medical Center & Nutrim School for Nutrition, Toxicology and Metabolism, Maastricht UniversityMaastricht
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19
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Schmidt SC, Hamann S, Langrehr JM, Höflich C, Mittler J, Jacob D, Neuhaus P. Preoperative high-dose steroid administration attenuates the surgical stress response following liver resection: results of a prospective randomized study. ACTA ACUST UNITED AC 2007; 14:484-92. [PMID: 17909718 DOI: 10.1007/s00534-006-1200-7] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2006] [Accepted: 10/10/2006] [Indexed: 12/29/2022]
Abstract
BACKGROUND/PURPOSE Major abdominal surgery such as liver resection is associated with an excessive hyperinflammatory response and transient immunosuppression. We investigated the immunomodulating effect of preoperative pulse administration of high-dose methylprednisolone in patients undergoing hepatic resection without pedicle clamping. METHODS Twenty patients who underwent hepatic resection were randomized into two groups: a steroid group (n = 10), in which patients were given 30 mg/kg per body weight (BW) methylprednisolone intravenously, and a control group (n = 10), in which patients received a placebo (sodium chloride) infusion. The main outcome parameter to assess systemic stress was the serum plasma level of interleukin-6 (IL-6). To evaluate cell-mediated immune function, human leukocyte antigen-DR (HLA-DR) expression on peripheral blood monocytes and lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) release by peripheral monocytes was measured. Other investigated serum parameters included C-reactive protein (CRP), total bilirubin, alanine aminotransferase (ALT), prothrombin time (PT)-INR, and cytokines such as IL-8 and IL-10 and TNF-alpha. Postoperative convalescence, complication rate, and length of hospital stay were compared between the groups. RESULTS Postoperative plasma concentrations of IL-6 (days 1 and 2), IL-8 (days 2 and 3), and CRP (days 1-4) were significantly lower in the steroid than in the control group. The total bilirubin concentration was significantly lower on day 6 in the steroid than in the control group. Four hours after surgery, LPS-induced TNF-alpha secretion was significantly reduced in the steroid group, but it increased rapidly during the following days. HLA-DR, ALT, and PT-INR levels were not different between the two groups. The postoperative hospital stay in the steroid group was significantly lower compared to that in the control group (mean, 10.5 days versus 14.8 days; P < 0.05). No differences were found in the convalescence score or postoperative complication rate. CONCLUSIONS Intravenous methylprednisolone administration before hepatic resection significantly reduced systemic inflammatory cytokine release. No adverse effect on immunity was noted due to the methylprednisolone. We found no significant difference in the convalescence score, but a significantly shorter hospital stay in the steroid group. Further studies with more patients are needed to elucidate the clinical impact of preoperative steroid bolus therapy in liver surgery.
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Affiliation(s)
- Sven C Schmidt
- Department of General-, Visceral- and Transplantation Surgery, University Medicine Berlin, Charité Campus Virchow Clinic, Augustenburger Platz 1, 13353 Berlin, Germany
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Raynaud JJ, Béchade D, Desrame J, Algayres JP. [Corticotherapy and giant hemangioma of the liver. Return to the normal values of cytokines]. ACTA ACUST UNITED AC 2006; 30:907-9. [PMID: 16885878 DOI: 10.1016/s0399-8320(06)73341-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
We report the case of a 36 year-old woman presenting with a giant liver hemangioma revealed by febrile hepatomegaly and weight loss. The patient presented an inflammatory syndrome without hyperleucytose, anemia and a moderate anicteric cholestasis. Plasma concentrations of interleukine-6 were very high whereas interleukine-1 levels were relatively low and TNF levels were normal. Eight weeks of corticosteroid treatment (prednisone 40 mg/d) resulted in disappearance of symptoms after 48 hours and biological anomalies after 6 weeks. Clinical and radiological follow-up, for respectively 36 and 24 months, did not show any relapse of symptoms or evolution of the hemangioma.
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21
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Fain JN, Tichansky DS, Madan AK. Transforming growth factor beta1 release by human adipose tissue is enhanced in obesity. Metabolism 2005; 54:1546-51. [PMID: 16253647 DOI: 10.1016/j.metabol.2005.05.024] [Citation(s) in RCA: 116] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2005] [Accepted: 05/23/2005] [Indexed: 01/04/2023]
Abstract
The present studies examined the effect of obesity in humans on the release of transforming growth factor beta1 (TGF-beta1) by human adipose tissue. The regulation of TGF-beta1 release by adipose tissue as well as the question of whether its release is due to the adipocytes or the nonfat cells in adipose tissue was also examined. There was a statistically significant (r=0.50) correlation between the body mass index of the fat donors and the subsequent release of TGF-beta1 release by subcutaneous adipose tissue. There was also a positive correlation between total TGF-beta1 release by adipose tissue explants and body fat content (r=0.69). The question of whether tumor necrosis factor alpha (TNF-alpha) and/or interleukin 1 beta (IL-1 beta) regulate the release of TGF-beta1 was investigated by incubation of adipose tissue explants with a soluble human TNF-alpha receptor (etanercept) and a neutralizing antihuman IL-1 beta antibody. The release of TGF-beta1 over 48 hours by adipose tissue explants was significantly enhanced in the presence of both the inhibitor of TNF-alpha and of IL-1 beta. It is of interest, in view of the elevated circulating insulin in blood of morbidly obese women, that the release of TGF-beta1 by adipose tissue was enhanced in the presence of insulin. The question of whether the release of TGF-beta1 by human adipose tissue explants was primarily due to adipocytes, as is the case for leptin, or the nonfat cells present in human adipose tissue, as is the case for IL-8 and prostaglandin E(2), was examined. The release of TGF-beta1 was primarily by the nonfat cells of human adipose tissue because release by adipocytes was less than 10% of that by the nonfat cells of adipose tissue.
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Affiliation(s)
- John N Fain
- Department of Molecular Sciences, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
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22
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Zhao X, Koshiba T, Fujimoto Y, Pirenne J, Yoshizawa A, Ito T, Kamei H, Jobara K, Ogawa K, Uryuhara K, Takada Y, Tanaka K. Proinflammatory and antiinflammatory cytokine production during ischemia-reperfusion injury in a case of identical twin living donor liver transplantation using no immunosuppression. Transplant Proc 2005; 37:392-4. [PMID: 15808656 DOI: 10.1016/j.transproceed.2004.12.272] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Bolus steroids are usually administered prior to graft reperfusion in an attempt to provide protection against ischemia reperfusion injury (IRI). However, the anti-IRI properties of steroids have not been established. Living donor liver transplantation (LDLT) between identical twins provides a unique opportunity to study the natural production of cytokines during transplantation without the confounding influences of the alloimmune response or of immunosuppression in particular steroids. METHODS A 38-year-old male with hepatitis C virus-related cirrhosis and multiple hepatocellular carcinomas received a hepatic right lobe graft from his identical twin. No immunosuppression was administered, not even intraoperative bolus steroids. IRI was assessed by serum transaminases as well as by proinflammatory interleukin (IL) IL-1beta, tumor necrosis factor (TNF)-alpha, IL-8 cytokines and for potent regenerative/anti-inflammatory (IL-6, IL-10) mediators. RESULTS Despite no administration of steroids, low peak levels of serum transaminases were observed. Serum IL-6 and IL-10 dramatically and rapidly increased during liver transplantation, namely, 160 and 20 times higher than baseline, respectively. In contrast, IL-1beta and TNF-alpha remained low during and after transplantation and an increase in IL-8 was less obvious. CONCLUSION Syngeneic LDLT without intraoperative bolus steroids is feasible, yielding no penalty in terms of IRI. A predominance of protective cytokines was observed in the absence of steroids. Thus, the concept that intraoperative administration of steroids is necessary to protect liver transplants from IRI must be revisited.
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Affiliation(s)
- X Zhao
- Department of Transplantation and Immunology, Transplant Tolerance Unit, Kyoto University, Faculty of Medicine, Kyoto, Japan
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Dahle MK, Øverland G, Myhre AE, Stuestøl JF, Hartung T, Krohn CD, Mathiesen Ø, Wang JE, Aasen AO. The phosphatidylinositol 3-kinase/protein kinase B signaling pathway is activated by lipoteichoic acid and plays a role in Kupffer cell production of interleukin-6 (IL-6) and IL-10. Infect Immun 2004; 72:5704-11. [PMID: 15385469 PMCID: PMC517537 DOI: 10.1128/iai.72.10.5704-5711.2004] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Sepsis caused by gram-positive bacteria lacking lipopolysaccharide (LPS) has become a major and increasing cause of mortality in intensive-care units. We have recently demonstrated that the gram-positive-specific bacterial cell wall component lipoteichoic acid (LTA) stimulates the release of the proinflammatory cytokines in Kupffer cells in culture. In the present study, we have started to assess the signal transduction events by which LTA induces the production of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and the anti-inflammatory cytokine IL-10 in rat Kupffer cells. LTA was found to trigger phosphorylation of mitogen-activated protein kinases (MAPK) (p38 MAPK and ERK 1/2) and protein kinase B (PKB). Compared to LPS, LTA was more potent in inducing PKB phosphorylation after 40 min, although we found that the cytokine responses were similar. For both bacterial molecules, blocking phosphatidylinositol 3-kinase (PI3-K; Ly294002) or Janus kinase 2 (JAK-2; AG490) particularly affected the induction of IL-6 and IL-10 release, whereas TNF-alpha levels were strongly reduced by inhibition of Src family tyrosine kinases (PP2). All three cytokines were reduced by inhibition of p38 MAPK (SB202190) or the broad-range tyrosine kinase inhibitor genistein, whereas IL-6 release was particularly blocked by inhibition of ERK 1/2 (PD98059). Divergences in the regulatory pathways controlling TNF-alpha, IL-10, and IL-6 production in Kupffer cells following LPS or LTA stimulation may create a basis for understanding how the balance between pro- and anti-inflammatory cytokines is regulated in the liver following infections by gram-positive or gram-negative bacteria.
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Affiliation(s)
- Maria K Dahle
- Institute for Surgical Research, Rikshospitalet University Hospital, N-0027 Oslo, Norway.
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