Pharmacological immunosuppression in clinical organ grafting. Observations on four agents: cyclosporin A, Asta 5122 (cytimun), lambda carrageenan and promethazine hydrochloride.

In this article I have attempted to summarize experiments on four agents investigated for immunosuppressive activity in experimental and clinical organ grafting. The difficulty of finding a suitable laboratory model relevant to man has been demonstrated in this experience. A cyclophosphamide-derivative, Asta-5122 (cytimun), has only a marginally superior immunosuppressive activity in a dog with a renal allograft compared with cyclophosphamide and is much inferior to azathioprine. This agent, however, appears to be valuable in clinical practice in patients with liver grafts. A combination of lambda carrageenan, promethazine hydrochloride and imuran has profound immunosuppressive activity in the same canine model, but proved to be both ineffective and potentially toxic in a limited trial in man. The fungal cyclic peptide, cyclosporin A, has been shown to be an extremely powerful immunosuppressive agent and remarkably non-toxic in dogs with renal allografts and pigs with orthotopic heart grafts. This agent is currently being investigated as an immunosuppressant in patients with organ grafts.