Prolongation of Graft Survival in Allogeneic Pancreas and Liver Transplantation by (–)15-Deoxyspergualin

Abstract

(–) 15-Deoxyspergualin, originally discovered as an antitumoral drug, was shown to have different immunosuppressive effects, when pancreas and orthotopic allogeneic liver transplantations in rats were compared. In the strong rejection model dark agouti → Lewis (RTl^a → RT1¹) we could only show a minor immunosuppressive effect, as far as pancreaticoduodenal and pancreas segment transplantations are concerned: graft survival was prolonged by 9 days in pancreas segment allografts (p < 0.01) and by 6 days in pancreaticoduodenal allografts (p < 0.01), when recipients were treated by ten doses of 2.5 mg/kg deoxyspergualin. Pretreatment of recipients with 15-deoxyspergualin was not efficient. On the contrary, in orthotopic liver transplantation done by the cuff technique, a remarkable prolongation of allograft survival could be demonstrated: about half of the animals showed prolongation of allograft survival for more than 80 days, compared with about 11 days in the control group (p < 0.01). The substance is considered to be valuable for clinical application.