A NEW IMMUNOSUPPRESSANT, FTY720, PROLONGS LIMB ALLOGRAFT SURVIVAL IN RATS

A new immunosuppressant, FP1720, was applied to limb allotransplants a nd its effectiveness was investigated. Using inbred rats, for which th e major histocompatibility complexes were completely mismatched, 31 li mb transplantations were performed and FTY720 was administered at a do se of 1.5 or 3 mg per kilogram per day for 10 days postoperatively. Re jection was monitored by the appearance of the skin of the grafted hin d limb, soft radiograph, microangiography, and histology, In animals r eceiving no immunosuppressive therapy, the mean onset of rejection was 4.2 +/- 1.0 days postoperatively, and the grafted limbs became acutel y necrotic, The mean onset of rejection was 6.0 +/- 0.9 days in animal s receiving FP1720 at a dose of 1.5 mg per kilogram per day and 7.9 +/ - 1.5 days in animals receiving FTY720 at a dose of 3 mg per kilogram per day. Survival of the grafted limbs was significantly prolonged com pared with that in animals without immunosuppression. The immunosuppre ssive effect of FTY720 appeared to be dose dependent; however, complet e suppression of rejection could not be obtained with FTY720 therapy a lone.