Exogenous interleukin-6 enhances the process of liver regeneration after liver transplantation in interleukin-6 knockout mice

Abstract

Objective To observe the effects of exogenous interleukin (IL)-6 on survival time and regeneration of liver grafts in an orthotopic liver transplantation model in IL-6 knockout (KO) mice.Methods A model of liver transplantation in C57BL/6 wild type (WT) and IL-6 KO mice with C57BL/6 background was established. Grafts were preserved at 4 ℃ in UW solution before transplantation.Study was divided into 4 groups:IL-6 KO→IL-6 KO control group,IL-6 KO→C57BL/6 WT group,IL-6 KO→IL-6 KO+ rIL-6 group,and IL-6 KO→C57BL/6 WT+ rIL-6 group.Recipient animals were injected subcutaneously with human recombinant IL-6 (1 mg/kg body weight) 1 h before transplantation.Survival of liver grafts after transplantation was followed up.Hepatocyte replication with BrdU uptake after liver transplantation was examined by irnmunohistochemistry.Results A total of 48 liver transplantations were performed.Cold ischemic time was 50 min.The survival time of liver grafts in the control group was 2.2 days,and that was 1.9 days,＞17.6 days and ＞20.4 days in IL-6 KO→C57BL/6 WT group,IL-6 KO+ rIL-6 group and C57BL/6 WT+ rIL-6 group respectively with the the difference being statistically significant among the latter three groups (P＜0.01 ).The liver grafts transplanted in control group recipients showed patchy areas of necrosis and hepatocyte ballooning.Slight increase in BrdU uptake was found at 48 h post-transplantation.Minimal injury and no necrosis were observed in IL-6 treated groups.Mild increase of BrdU uptake was demonstrated at 48 h after liver transplantation. Conclusion Exogenous recombinant IL-6 appears to significantly prolong the survival time of IL-6 KO liver grafts after liver transplantation and enhance the regenerative response after liver transplantation in IL-6 KO mice. Key words: Interleukin-6; Mice, knockout; Mice; Liver transplantation; Liver regeneration