ABROGATION OF SECOND-SET REJECTION WITH CYCLOSPORINE

Abstract

Cyclosporine was evaluated for its ability to delay or prevent accelerated rejection in a model of the secondset immune response. Lewis rats sensitized by LBN skin graft or subcutaneous heart fragments experienced accelerated rejection of heterotopic, vascularized LBN hearts with a mean survival time (MST) of approximately 5 days versus MST of 9.5 days for primary grafts. A short course of cyclosporine (10 mg/kg/day for 10 days) significantly prolonged graft survival in presensitized hosts to approximately 12 days (P < 0.01) as compared with the nontreated controls. Adjunctive splenectomy failed to further extend graft survival; MSTs were 12.0 and 5.7 days with and without cyclosporine, respectively. A comparable abrogation of second-set rejection was also achieved with a short course of antithy-mocyte serum (MST of 10.6 days). Rejection promptly ensued in all of the above groups shortly after cessation of immunosuppression. In contrast, a maintenance regimen of cyclosporine, given in a tapering dose, markedly extended graft survival to from 77 to 100+ days. Again, however, rejection eventually occurred following with-drawal of the cyclosporine. These data suggest that cyclosporine can indeed effectively prolong allograft survival in presensitized hosts.