PROLONGED SURVIVAL OF RAT SKIN ALLOGRAFT BY TREATMENT WITH FK506 OINTMENT

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Abstract
We studied the effect of FK506 ointment on rat skin allograft survival. Lewis rat (RT11) skin allografts were histologically evaluated on day 7 after transplantation to recipient ACI (RT1a) rats. We set histological gradings for rejection as follows: grade 1, intraepidermal blister formation; grade 2, incomplete epidermal separation from the dermis; and grade 3, complete epidermal separation from the epidermis. According to these histological criteria, the immunosuppressive effect of FK506 ointment was assessed. Our data indicated that all recipient rats without FK506 ointment showed grade 3 rejection on day 7 after transplantation. In contrast, the allografts treated with FK506 ointment showed grade 1 rejection. Furthermore the blood concentration of FK506 was below 0.5 ng/ml, minimizing the systemically adverse effects of FK506. Thus, the present study suggests that the topical administration of FK506 on the skin allografts may be useful and effective in the suppression of skin allograft rejection.