Effect of FK506 ointment (Protopic) on rat skin allograft model.

OBJECTIVE: FK-506 (tacrolimus) is a well known immunosuppressive agent used to prevent allograft rejection. The need for chronic allograft immunosuppression and the consequent harmful systemic effects preclude the use of tissue allograft as a routine surgical reconstructive option. This study assessed the effects of FK-506 ointment (Protopic) therapy versus subcutaneous injection of FK-506 (Prograf) on rat skin graft model.

METHODS: Donor Wistar rat dorsal skin was grafted to recipient Sprague-Dawley rats. Animals groups were divided into 2 groups: Group I was treated with intravenous injection of FK-506, and group II was treated with FK-506 ointment for 2 weeks after surgery. Graft appearance challenges were assessed.

RESULTS: FK506 ointment could prolong the median allograft survival time (16.7 days) compared with group I (15.8). Hematoxylin-eosin staining performed on the allo-skin biopsy samples obtained from both group I and II animals at 2 weeks after graft revealed moderate degree of skin rejection accompanied by mixed lymphocyte infiltration. Tacrolimus mean blood levels were much lower in group II (<0.2 ng/mL) than in group I (0.45 ng/mL) CONCLUSIONS: Immunosuppressive FK506 ointment therapy has similar effect to intravenous injection and it could be a useful therapy in the prevention of skin allograft rejection.