Cyclosporine in atopic dermatitis. Modulation in the expression of immunologic markers in lesional skin.

Abstract

In previous studies, oral cyclosporine was highly effective in the treatment of patients with severe atopic dermatitis. In this study seven patients with severe and therapy-resistant atopic dermatitis underwent therapy with cyclosporine, 5 mg/kg/day, for 6 weeks. The effect of cyclosporine on the expression of cytokines, which probably play a role in this disease, was examined. The study was performed with a panel of antibodies as markers of inflammatory cells, adhesion molecules, and cytokines (interferon-gamma [IFN-gamma], tumor necrosis factor-alpha [TNF-alpha] and interleukins 1 alpha, 1 beta, and 8 [IL-1 alpha, IL-1 beta, and IL-8, respectively]). They were visualized by indirect immunoperoxidase techniques. After 2 weeks of cyclosporine therapy, a reduction of 60% in the disease (severity and extent) was observed. This reduction was 89% after 4 weeks and 90% after 6 weeks of therapy. Results of indirect immunoperoxidase stains performed on lesional skin sections after 2 weeks of treatment showed statistically significant reduced numbers of CD14+, CD25 (IL-2R+) and IL-8+ inflammatory cells in the dermis and CD36(OKM5)+ cells in both the epidermis and dermis. The number of cells expressing IFN-gamma and TNF-alpha, assumed to be the products of the helper T-cell (TH)1 subset, was unaltered despite the impressive clinical benefit observed. Keratinocytes in lesional atopic skin did not express intercellular adhesion molecule type 1 (ICAM-1). The expression of the adhesion molecules ICAM-1, lymphocyte function-associated (LFA) type 1, and LFA-3 on inflammatory cells also remained unaffected by cyclosporine treatment. A statistically significant reduction in the number of activated T cells and in the number of cells expressing the IL-2 receptor (CD25) paralleled a marked improvement in the disease and supports the view that atopic dermatitis is based on a T-cell-mediated immune inflammation.