Long-term survival of skin allografts in rats treated with topical cyclosporine.

Abstract

The use of topical cyclosporine (CsA) was studied in skin allografts from Buffalo to Lewis rats. CsA prepared in olive oil and dimethyl sulfoxide was administered in various dosages topically on allografts. Untreated allografts were rejected in 7.4 +/- 1.1 days but survived for 18.6 +/- 0.9, 29.3 +/- 1.8, or 40.6 +/- 2.2 days after 10, 20, or 28 days of topical CsA treatment (10 mg/rat/day), respectively. Long-term graft survival (greater than 100 days) was seen with continuous CsA treatment at 10 mg/rat/day, 10 mg/rat/2 days, and 5 mg/rat/day, as compared with rejection in 13.1 +/- 2.3 and 8.9 +/- 0.9 days with CsA 10 mg/rat/3 days and 5 mg/rat/2 days, respectively. The therapeutic blood level of CsA ranged from 250 to 500 ng/ml. Most grafts were rejected when CsA blood levels fell below 200 ng/ml. Direct administration of topical CsA onto the allografts resulted in longer survival compared with those applied on the normal recipient skin 6 cm distal to the allografts, with both high and low doses. Locally high concentrations of CsA in allografts may play an important role in prolongation of graft survival. Minimal cell infiltration and loss of hair follicles were the main histological features in long-surviving allografts (greater than 120 days).