Y E Kim1, S-C Eun2. 1. Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Korea. 2. Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Korea. Electronic address: sceun@snubh.org.
Abstract
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.
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.