Effect of FK 506 and lipo prostaglandin E1 on heart allograft survival in rats

FK 506 (FK) has a strong immunosuppressive effect, but a low-grade, dose-dependent nephrotoxicity and diabetogenicity, which means that reducing the dose of FK is of considerable interest. Lipo-prostaglandin E-1 (LPGE(1)) is a preparation of PGE(1) that has potent immunosuppressive properties, and its 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 immunosuppressive effect of FK. Heterotopic cardiac transplantations to the neck vessels were performed, and recipient rats were treated with intramuscular injections of FK and LPGE(1) once daily for 10 days. All grafts without any treatment 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 graft survival (>100 days) to 8%, 44% and 100%, respectively. The addition of LPGE(1) to the first two dosages caused a further significant increase in the graft survival, to 18% and 80%, respectively, when compared with the control. LPGE(1) appears to enhance the immunosuppressive effect of FK.