A COMPARATIVE INVESTIGATION OF FK506 AND CYCLOSPORINE-A IN MURINE CORNEAL TRANSPLANTATION

Background: Acute rejection is the cause of over 50% of transplant opa cifications in some immunological high-risk groups. More potent immuno modulating substances must be found in order to allow extended or indi vidualised therapeutic options for combating rejection. Methods: Rats of the inbred strains Brown Norway and Lewis were used as donors and r ecipients, respectively. FK506 (Prograf) was administered intraperiton eally for 14 days in a dosage of 0.3 mg/kg bw, and cyclosporin A (CSA; Sandimmun) was administered, likewise for 14 days, in an intramuscula r dosage of 10 mg/kg bw. The transplants were examined every 3rd day b y slit-lamp microscopy. Every transplant was subjected to histological or immunohistological evaluation, Results: The average transplant sur vival period in the allogeneic strain combination was 7.9 days (SEM=1. 1). Therapy with FK506 led to a statistically significant prolongation of transplant survival to 17.1 days (SEM=1.5, P<0.05). Therapy with C SA delayed transplant rejection to 21 days (SEM=0.0, P<0.05). No stati stically significant difference was found between the two therapeutic regimens. There were no significant histomorphologic differences in re jected grafts in the FK506- and CSA-treated animals, a Conclusions: In this study we have shown that FK506 is able to delay corneal allograf t rejection at a much lower dosage than CSA without a higher incidence of side effects related to toxicity or overimmunosuppression.