| Objective To investigate the immunosuppressive effects and related mechanism of XGD-1. Methods In vitro ,by means of lymphocyte transformation test, the effect of XGD-1, Neoral, XGD-1+ Neoral of different concentration on ConA-induced rat splenocyte proliferation was observed; in vivo, 80 Sprague-Dawley rats after intrasplenic allogeneic hepatocyte transplantation were divided into 4 groups: olive oil treated group, XGD-1 treated group, Neoral treated group, XGD-1 plus demi-dose Neoral treated group, each group had 20 rats, and 5 rats were used as normal group(untreated group). The level of IL-1 a and IL-2 in blood serum were measured on l,3,5,7day post operation. At the same time, tissue samples were taken from the spleen, fixed in 10% neutral buffered formalin, and 5um sections were stained with hematoxylin-eosin (H&E) for histopathology observation. Results XGD-1 can significantly inhibit lymphocyte proliferation contrast to control group (p<0.01) and the inhibition rate was higher with the raise of drug concentration(from 26.28% to 60.95%). Be contrasted to Neoral(2μg/ml and 1μg/ml), XGD-1 plus Neoral((lμg/ml XGD-1 plus 2μg/ml Neoral and lμg/ml XGD-1 plus 5μg/ml Neoral) showed more effective. After hepatocyte transplantation , a significant increase in the level of IL-1 a and IL-2 was observed. However, the two index could be decreased notably after the use of XGD-1 since postoperation 3d and 5drespectively. Since posttransplantation 5d, there was a more obvious fall in the level of IL-1 α when demi-dose Neoral was added contrast to omni-dose Neoral treated group and the degree of IL-2 was close between the two groups since 5d posttransplantation. Conclusion XGD-1 could inhibit lymphocyte proliferation effectively in vitro . To IL-1α, XGD-1 showded a more significant decrease than Neoral; while to IL-2, Neoral had a more inhibitory effect on it in vivo. We conferred that there was a synergistic action between XGD-1 and Neoral. The main target cell of XGD-1 was monocyt/macrophage, while the Neoral was T lymphocyte. XGD-1 and Neoral relieved response intensity of inflammation and rejection via the interaction among cytokines. XGD-1 had a stronger effect on controlling inflammation and Neoral was more sensitive to the activation of T lymphocyte. |