Disappearance rates and immunosuppression of intermittent intravenously administered prednisolone in rabbits and human beings.

Abstract

Full thickness skin grafts were exchanged between 16 New Zealand and 16 California rabbits. Intramuscularly administered methylprednisolone prolonged the average survival of the grafts from 8.5 to 12.6 days when given in doses of 0.1 milligram per kilogram per day and to 14.8 days when given in doses of 0.25 milligram per kilogram per day. When single injections of 10 milligrams per kilogram were added intravenously every six days to the lesser of the foregoing maintenance doses, the graft survived an average of 15.5 days. Six normal volunteers and ten patients with variable renal function were given an intravenous infusion of 1 gram of prednisolone over 60 minutes The plasma steroid levels rose to prodigious heights, but then returned to normal within 12 to 24 hours, by an elimination process that was not dependent on renal function. Lymphopenia was produced along with variable changes in the total white blood count. The expression of delayed hypersensitivity to mumps, Candida, tuberculin, and vaccinia antigens was either prevented or weakened for at least the first day after the steroid injection. These experiments support the validity of a clinical practice that has developed more or less empirically in the treatment of homograft recipients, namely the intermittent intravenous administration of large quantities of steroids as a supplement to low maintenance doses. The additional immunosuppressive effect thereby achieved cannot be explained simply by a persistence of plasma steroid levels between the special infusions since the disappearance of the intravenously administered prednisolone occurs too rapidly.