Early Studies of Local Immunosuppression (1964–1984)

The possibility that regional administration of a drug might prolong the survival of transplanted tissue arose during the early 1950s, when Billingham et al1 treated rabbit skin allografts with 5 mg of cortisone acetate suspended in 0.2 ml of saline with 1.5% benzyl alcohol. This suspension was applied directly to the grafted skin every third day, beginning immediately before the grafts were placed on the prepared site. The topical application of cortisone more than doubled the survival time of the allografts, while systemic administration of the same quantity of cortisone on the same schedule was completely ineffective in delaying rejection. Although the potential clinical advantage of applying cortisone locally in quantities that would inhibit the rejection response and simultaneously avoid deleterious systemic side effects was apparent to these investigators, the idea languished until the next decade.