EFFECT OF CYCLOSPORINE-A ON THE REGULATION OF IA-ANTIGEN KERATINOCYTES EXPRESSION

Since many skin diseases characterized by positive Ia keratinocytes show improvement with cyclosporine therapy, the purpose of this study was to determine whether cyclosporine A (CyA) alters the expression of Ia keratinocytes. Nude mice were injected with normal mouse serum (NMS) to induce keratinocyte expression of the Ia antigen. The injected mice were then divided into four groups: one was treated with oral CyA; the second was treated topically with CyA twice a day; the third was treated topically with olive oil; and the fourth was injected with nude mouse serum. The third and fourth groups served as Ia positive and Ia negative controls, respectively. The mice were treated during the first 10 days after the injections. On Day 10, epidermal sheets were analyzed for Ia expression. Analysis was made by an indirect immunoperoxidase staining method using monoclonal antibodies specific for Ia determinants. Quantitation of the number of Langerhans cells was analyzed on epidermal sheets using immunodiagnostic reagents, anti-MHC-Ia, and surface ectoenzyme, ATPase. A significant reduction of Ia-positive keratinocytes was noted in the oral CyA group vs topical and olive oil groups (64.9 ± 29.9% vs 20.1 ± 18.7%, respectively, P < 0.01). In a second set of experiments mice were injected with NMS, but treatment was started only on Day 10 after injections, for 10 days. The results showed that CyA failed to down-regulate Ia expression. Topical and systemic CyA did not modify Langerhans cell population. The present study showed that systemic administration of CyA significantly reduced Ia induction by keratinocytes of nude mice that were injected with NMS. © 1991.