Effect of FK 506 and lipo prostaglandin E-1 on heart allograft survival inrats

FK 506 (FK) has a strong immunosuppressive effect, but a low-grade, dose-de pendent nephrotoxicity and diabetogenicity, which means that reducing the d ose of FK is of considerable interest. Lipo-prostaglandin E-1 (LPGE(1)) is a preparation of PGE(1) that has potent immunosuppressive properties, and i ts duration of action is longer than that of ordinary PEGE(1). The purpose of this study was to investigate whether LPGE(1) can enhance the immunosupp ressive effect of FK. Heterotopic cardiac transplantations to the neck vess els were performed, and recipient rats were treated with intramuscular inje ctions of FK and LPGE(1) once daily for 10 days. All grafts without any tre atment were rejected within 14 days. In comparison, the FK doses of 0.07, 0 .2 and 1.0 mg/kg/day for 10 days significantly increased the long-term graf t survival (>100 days) to 8%, 44% and 100%, respectively. The addition of L PGE(1) to the first two dosages caused a further significant increase in th e graft survival, to 18% and 80%, respectively, when compared with the cont rol. LPGE(1) appears to enhance the immunosuppressive effect of FK.