The Effect of Supralethal Amethopterin and Folinic Acid Rescue on Mouse Skin Allograft Survival1

The folic acid antagonist amethopterin has been utilized as an immunosuppressive agent in mice in supralethal dosages combined with delayed administration of folinic acid as a rescuing agent. This principle has been found effective in significantly prolonging the survival of skin grafts involving major histocompatibility differences. A schedule of injections of 30 mg/kg body weight given subcutaneously, with a 200 mg/kg folinic acid rescue intraperitoneally 6 hr later, given every 5 days, allowed maximum graft survival of up to 18 days. Pre-graft treatment was found to be without effect, and previous thymectomy seemed to exert a “protective” effect against both the therapeutic and toxic manifestations of amethopterin therapy.