EFFECT OF PERITRANSPLANT FTY720 ALONE OR IN COMBINATION WITH POSTTRANSPLANT TACROLIMUS IN A RAT MODEL OF CARDIAC ALLOTRANSPLANTATION

FTY720 is a recently discovered compound that is derived from the fung us Isaria sinclairii. Using a DA donor-to-LEW recipient rat combinatio n, we assessed the efficacy of peritransplant FTY720 alone or in combi nation with posttransplant tacrolimus on the survival of cardiac allog rafts. Peritransplant FTY720 given orally at a dose of 5 mg/kg on days -1 and 0 prolonged graft survival from 5 to 13 days (P < 0.05). Combi ning peritransplant FTY720 with post-transplant tacrolimus resulted in a further prolongation of allograft survival. The lymphocyte count in transplanted rats decreased within 24 h to 46.6 %. Analysis of lympho cyte subsets by FAGS revealed that FTY720 affected the total populatio n of CD3-bearing T cells while the ratio of CD4 to CD8 cells remained unchanged. Kidney and liver biochemistry remained elevated for 2 weeks . In conclusion, FTY720 is a powerful immunosuppressive agent when use d as induction therapy and may have an additive effect - perhaps a syn ergistic one - with post-transplant tacrolimus.