Effect of 1,25-dihydroxyvitamin D3 on preventing allograft from acute rejection following rat orthotopic liver transplantation.

ABSTRACT

AIM: To study the mechanism and the preventive role of 1,25-dihydroxyvitamin D3 in acute rejection following orthotopic liver transplantation. METHODS: Rats were randomly divided as donors or recipients for orthotopic liver allotransplantation model. Four groups were designed in the study, Group I syngenic control (Wistar to Wistar); Group II acute rejection (SD to Wistar); Group III acute rejection treated with cyclosporine A, and Group IV acute rejection treated with 1,25-(OH)2D3. Liver function, rejection activity index and mRNA of IFN-gamma, IL-10 in intragraft in recipients were measured in on day 1, 5, 7, 15, 30 posttransplant for assessing graft function, severity of acute rejection and immune state of recipients. RESULTS: Survival time of recipients in Group VI was significantly prolonged (over 100 days) in comparison with other groups (vs Group II, P<0.001; vs Group III, P>0.05). After treatment with 1,25-(OH)2 D3, mean value of all the assay tested on each experimental time was compared, liver function in group IV was significantly improved (AST 127+/-41 U/L-360+/-104 U/L, BIL 13+/-5 mmol/l-38+/-11 mmol/l; vs Group II, P<0.05; vs Group III, P>0.05. Rejection activity index was significantly decreased (0-3.3+/-1.6; vs Group II, P<0.05; vs Group III, P>0.05). Level of hepatic IFN-gamma mRNA in group IV was decreased, while level of hepatic IL-10 mRNA was increased (vs Group II, P<0.05; vs Group III, P>0.05). CONCLUSION: Our results indicated that 1,25-(OH)2D3 induced the secretion of cytokine toward to Th2 type, which would alleviate acute rejection, protect liver function and prolong survival of recipient after orthotopic liver transplantation.