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.
D000328:Adult; D000818:Animals; D001379:Azathioprine / Q000494:pharmacology / Q000627:therapeutic use; D002351:Carrageenan / Q000494:pharmacology / Q000627:therapeutic use; D003498:Cyclic P-Oxides / Q000494:pharmacology / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000031:analogs & derivatives; D004285:Dogs; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016030:Kidney Transplantation; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000494:pharmacology / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use; D011398:Promethazine / Q000494:pharmacology / Q000627:therapeutic use; D013552:Swine; D014184:Transplantation, Homologous
D003498:Cyclic P-Oxides; D007166:Immunosuppressive Agents; D010078:Oxazines; D010456:Peptides, Cyclic; C006188:sufosfamide; D003520:Cyclophosphamide; D002351:Carrageenan; D011398:Promethazine; D001379:Azathioprine