Gemcitabine - A novel immunosuppressive agent - Prevents rejection in a rat cardiac transplantation model

Background, 2',2'-difluorodeoxycytidine (dFdC, gemcitabine) is a pyrimidine antimetabolite with antineoplastic activity against a wide range of solid tumors. The immunosuppressive activities of this compound have not been des cribed to date. Methods. The in vitro effects on activated T lymphocytes were studied with a lymphocyte colony-forming assay in a microagar culture system. Heart tran splantations were performed in the fully allogeneic Lewis/Brown Norway comb ination. dFdC was administered once daily at various dosages from the time of surgery until day 50, Results. Phytohemagglutinin-induced lymphocyte proliferation was inhibited 50% by dFdC at a concentration of 3.25 +/- 0.9 nmol/L, Allografts of untrea ted animals survived for 7.5 (7-8) days and those with 25, 50, and 75 mu g/ kg body weight dFdC for 7.3 (7-8), 9.3 (8-10), and 16.3 (10-38) days, respe ctively. Treatment with 100 or 125 mu g/kg body weight of dFdC, however, pr olonged allograft survival until day 152.8 (129-178), Dose-dependent leukop enia was the main toxicity. Conclusions, DFdC is a new immunosuppressive agent that can successfully pr event cardiac rejection in a rat transplantation model.