Interleukin-6 expression in rhesus monkey models with acute rejection after liver transplantation

doi:10.3969/j.issn.2095-4344.2014.36.004

Abstract

Abstract:

BACKGROUND: Interleukin-6 is an important cytokine in the immune inflammatory response, strongly links with graft rejection reaction, and plays an important role in diagnosis of graft rejection and evaluation of anti-rejection.
OBJECTIVE: To measure the expression of interleukin-6 in acute rejection of the liver transplantation in the rhesus monkey, and to evaluate the value as an early diagnosis of acute rejection after liver transplantation.
METHODS: A total of 16 rhesus monkeys were used as the object and randomly divided into experimental group (no treated by immunosuppressant in perioperative period), and control group (treated by immunosuppressant in perioperative period). The allograft orthotopic liver transplantation models were established in those monkeys. Then serum and liver tissue were collected at 6, 12, 24, and 72 hours after surgery. Allograft rejection was monitored by liver function tests, and hematoxylin-eosin staining of liver and Banff score. Finally, the expression levels of interleukin-6 were detected by enzyme linked immunosorbent assay and immunohistochemistry.
RESULTS AND CONCLUSION: Acute graft rejection reaction appeared at 12, 24 and 72 hours after liver transplantation in the experimental group. The expressions of alanine aminotransferase, aspartate aminotransferase and total bilirubin were significantly higher in the experimental group than in the control group at 24 and 72 hours (P < 0.05). Histological manifestations were severer and Banff score was higher in the experimental group at 72 hours than in the control group (P < 0.05). Interleukin-6 levels were significantly higher in the serum and liver tissue of experimental group than in the control group at 12, 24 and 72 hours after liver transplantation (P < 0.05), especially at 72 hours. Results suggested that interleukin-6 possibly participated in rejection after liver transplantation. The expression of interleukin-6 was probably of significance in the early diagnosis of acute rejection after orthotopic liver transplantation in rhesus monkeys.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

全文链接：

Key words: liver transplantation, graft rejection, interleukin-6, macaca mulatta, early diagnosis

CLC Number:

R318

Ran Jiang-hua, Zhang Xi-bing, Liu Jing, Zhang Sheng-ning, Li Lai-bang, Gao Yang, Chen Yi-ming, Li Wang, Li Li . Interleukin-6 expression in rhesus monkey models with acute rejection after liver transplantation[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(36): 5758-5763.

Figures/Tables 4

References

[1] Xie XJ, Ye YF, Zhou L,et al. Th17 promotes acute rejection following liver transplantation in rats. J Zhejiang Univ Sci B. 2010;11(11):819-827.
[2] Casas-Melley AT, Falkenstein KP, Flynn LM,et al. Improvement in renal function and rejection control in pediatric liver transplant recipients with the introduction of sirolimus. Pediatr Transplant. 2004;8(4):362-366.
[3] Mas VR, Fisher RA, Maluf DG,et al. Polymorphisms in cytokines and growth factor genes and their association with acute rejection and recurrence of hepatitis C virus disease in liver transplantation.Clin Genet. 2004;65(3): 191-201.
[4] Cueto-Manzano AM, Morales-Buenrostro LE, González-Espinoza L,et al. Markers of inflammation before and after renal transplantation.Transplantation. 2005;80(1): 47-51.
[5] Boniface K, Lecron JC, Bernard FX,et al. Keratinocytes as targets for interleukin-10-related cytokines: a putative role in the pathogenesis of psoriasis.Eur Cytokine Netw. 2005;16(4): 309-319.
[6] Murano M, Maemura K, Hirata I,et al. Therapeutic effect of intracolonically administered nuclear factor kappa B (p65) antisense oligonucleotide on mouse dextran sulphate sodium (DSS)-induced colitis. Clin Exp Immunol. 2000; 120(1):51-58.
[7] 冉江华,张升宁,刘静,等.恒河猴同种异体原位肝移模型的改进[J].中国普外基础与临床杂志,2010,17(7):694-698.
[8] 冉江华,李铸,刘静,等.二袖套法建立恒河猴原位肝移植的稳定模型[J].中国组织工程研究与临床康复,2011,15(5):762-768.
[9] Busuttil RW, Lake JR. Role of tacrolimus in the evolution of liver transplantation. Transplantation. 2004;77(9 Suppl): S44-51.
[10] Solez K. History of the Banff classification of allograft pathology as it approaches its 20th year.Curr Opin Organ Transplant. 2010;15(1):49-51.
[11] Racusen LC, Halloran PF, Solez K. Banff 2003 meeting report: new diagnostic insights and standards.Am J Transplant. 2004; 4(10):1562-1566.
[12] Girnita DM, Burckart G, Zeevi A. Effect of cytokine and pharmacogenomic genetic polymorphisms in transplantation. Curr Opin Immunol. 2008;20(5):614-625.
[13] Cordero-Pérez P, Torres-González L, Muñoz-Espinosa LE. Cytokines expression in peripheral blood cells of patients with orthotopic liver transplant: preliminary results. Rev Gastroenterol Mex. 2011;76(2):108-112.
[14] Yao J, Feng XW, Yu XB,et al. Recipient IL-6-572C/G genotype is associated with reduced incidence of acute rejection following liver transplantation.J Int Med Res. 2013; 41(2):356-364.
[15] Ravaglia G, Forti P, Maioli F, et al. Associations of the -174 G/C interleukin-6 gene promoter polymorphism with serum interleukin 6 and mortality in the elderly.Biogerontology. 2005;6(6):415-423.
[16] Tono T, Monden M, Yoshizaki K,et al. Biliary interleukin 6 levels as indicators of hepatic allograft rejection in rats. Transplantation. 1992;53(6):1195-1201.
[17] Kita Y, Iwaki Y, Demetris AJ,et al. Evaluation of sequential serum interleukin-6 levels in liver allograft recipients. Transplantation. 1994;57(7):1037-1041.
[18] Kunz D, Pross M, König W,et al. Diagnostic relevance of procalcitonin, IL-6 and cellular immune status in the early phase after liver transplantation.Transplant Proc. 1998;30(5): 2398-2399.
[19] Boros P, Suehiro T, Curtiss S,et al. Differential contribution of graft and recipient to perioperative TNF-alpha, IL-1 beta, IL-6 and IL-8 levels and correlation with early graft function in clinical liver transplantation.Clin Transplant. 1997;11(6): 588-592.
[20] Afzali B, Lombardi G, Lechler RI,et al. The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease.Clin Exp Immunol. 2007;148(1):32-46.
[21] Függer R, Hamilton G, Steininger R,et al. Intraoperative estimation of endotoxin, TNF alpha, and IL-6 in orthotopic liver transplantation and their relation to rejection and postoperative infection.Transplantation. 1991;52(2): 302-306.
[22] Ohzato H, Yoshizaki K, Nishimoto N,et al. Interleukin-6 as a new indicator of inflammatory status: detection of serum levels of interleukin-6 and C-reactive protein after surgery. Surgery. 1992;111(2):201-209.
[23] Tilg H, Nordberg J, Vogel W,et al.Circulating serum levels of interleukin 6 and C-reactive protein after liver transplantation. Transplantation. 1992;54(1):142-146.
[24] Debonera F, Aldeguer X, Shen X,et al. Activation of interleukin-6/STAT3 and liver regeneration following transplantation.J Surg Res. 2001;96(2):289-295.
[25] Kutukculer N, Clark K, Rigg KM,et al. The value of posttransplant monitoring of interleukin (IL)-2, IL-3, IL-4, IL-6, IL-8, and soluble CD23 in the plasma of renal allograft recipients.Transplantation. 1995;59(3):333-340.
[26] Gorczynski RM, Adams RB, Levy GA,et al. Correlation of peripheral blood lymphocyte and intragraft cytokine mRNA expression with rejection in orthotopic liver transplantation.Surgery. 1996;120(3):496-502.
[27] Takai Y, Wong GG, Clark SC,et al. B cell stimulatory factor-2 is involved in the differentiation of cytotoxic T lymphocytes.J Immunol. 1988;140(2):508-512.
[28] Brouckaert P, Spriggs DR, Demetri G,et al. Circulating interleukin 6 during a continuous infusion of tumor necrosis factor and interferon gamma. J Exp Med. 1989;169(6):2257- 2262.
[29] Cho KA, Lim GW, Joo SY, et al. Transplantation of bone marrow cells reduces CCl4 -induced liver fibrosis in mice. Liver Int. 2011;31(7):932-939.
[30] Ren X, Hogaboam C, Carpenter A,et al. Stem cell factor restores hepatocyte proliferation in IL-6 knockout mice following 70% hepatectomy.J Clin Invest. 2003;112(9):1407- 1418.