Inhibited differentiation of Langerhans cells in the rat epidermis upon systemic treatment with cyclosporin A

The immunosuppressant drug cyclosporin A (CsA) is known to cause reduction in number, DNA synthesis and function of Langerhans cells (LC). Since also the differentiation of LC is known to be hampered in conditions of acquired immunodeficiency not due to drugs, we investigated whether this occurs wit h CsA. Rats were injected subcutaneously with CsA (5, 10 and 50 mg.kg(-1).d (-1)) for three weeks; the skin was analyzed by Ia immunohistochemistry and by electron microscopy. Epidermal immunolabeled cells were 15+/-3.5 (mean +/- SEM) per 100 basal keratinocytes in untreated controls and 8.75+/-1.3, 4.75+/-1.0 and 1.7+/-1.2 upon increasing doses of CsA (p<0.01). By electron microscopy, monocytoid cells with deep invaginations of the plasma membran e and roundish LC poor in Birbeck granules appeared in the epidermis upon t reatment. The results suggest that CsA inhibits the differentiation of LC p recursors in the epidermis and that this can in part explain the selective increase in the risk of skin viral disease and cancer in chronically treate d patients.