PREVENTION OF GRAFT-REJECTION AND GRAFT-VERSUS-HOST REACTION BY A NOVEL IMMUNOSUPPRESSANT, FTY720, IN RAT SMALL-BOWEL TRANSPLANTATION

In the present study, we examined the immunosuppressive effect of a ne w drug, FTY 720, on small bowel transplantation (SET) in rats. Grafts from (LEW x BN) F1-to-LEW rats treated with FTY 720 at 0.5 mg/kg from day 0 to 14 post-SET survived significantly longer than untreated graf ts. In addition, the administration of FTY 720 combined with cyclospor in (CyA; 5 mg/kg per day) had a synergistic effect on allograft surviv al. The graft-versus-host reaction (GVHR) that occurred in the LEW-to- F1 rats was markedly reduced after the administration of FTY 720. FTY 720 combined with a low dose of CyA completely abrogated GVHR without any adverse reaction. FTY 720 treatment resulted in a significant decr ease in the number of lymphocytes in the peripheral blood and the sple en, but the number of peripheral neutrophils was unchanged. Thus, FTY 720 would appear to be an ideal drug to combine with CyA in order to c ontrol the immune reaction after SBT.