Advances in immunosuppressive drugs have improved the short-term survival of liver transplantation. However, drug toxicities have been a serious problem in patients after long-term administration. Therefore, it is necessary to develop a novel immunosuppressant with low-toxicity. We investigated the immunosuppressive effects of Emodin on acute graft rejection following liver transplantation in rats. The recipient rats of orthotopic liver transplantation were divided into groups as follows: isograft+NS group, allograft+NS group, and allograft+emodin group. The survival time of the recipients in each group was recorded. Histopathological changes in the liver, as well as serum concentrations of IL-2, TNF-α, and IL-10 and their expressions in liver tissue were determined. Our results showed that Emodin treatment prolonged liver allograft survival time and inhibited histopathologic changes of acute graft rejection. The rejection activity index in groups isograft+NS, allograft+NS, and allograft+emodin were 1.52 ± 0.37, 6.95 ± 0.75, and 4.23 ± 0.51, respectively (P < 0.01, isograft+NS group vs. allograft+emodin group and allograft+NS group vs. allograft+emodin group). The serum levels of IL-2 and TNF-α were down-regulated but that of IL-10 was up-regulated by Emodin. Serum levels of IL-2 and TNF-α were higher in allograft+NS group than the allograft+emodin group, but that of IL-10 showed opposite effects (P < 0.05 or 0.01). Changes in the expression of these cytokines in transplanted liver tissue were consistent with changes in serum concentrations. These results demonstrate that Emodin has therapeutic potentials for alleviating acute rejection following liver transplantation in rats and prolonging liver allograft survival. The mechanisms underlying this effect may be associated with polarizing the Th1/Th2 paradigm to Th2.
Copyright © 2011 Wiley-Liss, Inc.