BACKGROUND: Acute rejection is the cause of over 50% of transplant opacifications in some immunological high-risk groups. More potent immunomodulating substances must be found in order to allow extended or individualised therapeutic options for combating rejection. METHODS: Rats of the inbred strains Brown Norway and Lewis were used as donors and recipients, respectively. FK506 (Prograf) was administered intraperitoneally 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 intramuscular dosage of 10 mg/kg bw. The transplants were examined every 3rd day by slit-lamp microscopy. Every transplant was subjected to histological or immunohistological evaluation. RESULTS: The average transplant survival 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 CSA delayed transplant rejection to 21 days (SEM = 0.0, P < 0.05). No statistically significant difference was found between the two therapeutic regimens. There were no significant histomorphologic differences in rejected grafts in the FK506- and CSA-treated animals. CONCLUSIONS: In this study we have shown that FK506 is able to delay corneal allograft rejection at a much lower dosage than CSA without a higher incidence of side effects related to toxicity or overimmunosuppression.
BACKGROUND: Acute rejection is the cause of over 50% of transplant opacifications in some immunological high-risk groups. More potent immunomodulating substances must be found in order to allow extended or individualised therapeutic options for combating rejection. METHODS:Rats of the inbred strains Brown Norway and Lewis were used as donors and recipients, respectively. FK506 (Prograf) was administered intraperitoneally 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 intramuscular dosage of 10 mg/kg bw. The transplants were examined every 3rd day by slit-lamp microscopy. Every transplant was subjected to histological or immunohistological evaluation. RESULTS: The average transplant survival 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 CSA delayed transplant rejection to 21 days (SEM = 0.0, P < 0.05). No statistically significant difference was found between the two therapeutic regimens. There were no significant histomorphologic differences in rejected grafts in the FK506- and CSA-treated animals. CONCLUSIONS: In this study we have shown that FK506 is able to delay corneal allograft rejection at a much lower dosage than CSA without a higher incidence of side effects related to toxicity or overimmunosuppression.