HISTOINCOMPATIBLE SKIN AND MARROW GRAFTS IN RABBITS ON CYCLOSPORIN A

Abstract

Cyclosporin A (Cy A; 15 mg/kg s.c.) allows allogeneic histoincompatible skin graft survival in 10 of 10 rabbits as long as the drug is given. The same dose of Cy A does not affect acute graft-vs.-host disease (GVHD) and increased survival of rabbits after allogeneic bone marrow transplantation between the same 2 strains, when 2 groups of 15 animals are tested. Median survival of 14 engrafted animals without Cy A was 23 days and of 12 engrafted animals with Cy A 22 days (not significant). Cryopreservation of bone marrow delays the onset of GVHD and increases survival of engrafted animals. Median survival of 5 engrafted animals without Cy A was 33 days and of 14 engrafted animals with Cy A 35 days. One part of early GVHD as well as of eary graft rejection probably is mediated by a subclass of cells which is resistant to Cy A. This hypothesis is supported by the finding that most transplanted skins show a self-limited period of infiltration and induration. Skin grafts survive this period of infiltration. If the same potentially self-limited process occurs in the liver or the intestine during acute GVHD, animals die. This hypothesis could explain why Cy A allows skin graft survival but does not affect acute GVHD.