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 E1 (LPGE1) is a preparation of PGE1 that has potent immunosuppressive properties, and its duration of action is longer than that of ordinary PGE1. The purpose of this study was to investigate whether LPGE1 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 LPGE1 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 LPGE1 to the first two dosages caused a further significant increase in the graft survival, to 18% and 80%, respectively, when compared with the control. LPGE1 appears to enhance the immunosuppressive effect of FK.
Uchino
T
T
Department of Thoracic and Cardiovascular Surgery, Sahlgrenska University Hospital, University of Gothenburg, Sweden.
Belboul
A
A
Olausson
M
M
Mjörnstedt
L
L
Roberts
D
D
Berglin
E
E
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007273:Injections, Intramuscular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016559:Tacrolimus / Q000494:pharmacology*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D000527:Alprostadil; D016559:Tacrolimus