Influence of systemic cyclosporin A on interleukin-2 and epidermal growth factor receptor expression in psoriatic skin lesions

Lesional and non-lesional skin biopsies from patients with chronic plaque psoriasis receiving systemic cyclosporin A (CyA; 2.5 or 5 mg/kg(-1) per day) were examined for changes in T cell populations, Langerhans cells and the expression of interleukin-2 (IL-2) and epidermal growth factor receptors (EGFR) by immunohistochemistry. After 4 weeks of treatment a striking reduction in disease activity was observed, accompanied by a marked reduction in the numbers of CD4+ and CD8+ cells in the epidermis and dermis. As early as 7 days after initiation of treatment, a substantial reduction in the number of CD4+ lymphocytes in the dermis was detected. At the same time there was a significant reduction in the number of cells expressing IL-2 receptors (IL-2R); this was greater than the corresponding decrease in CD3+ cells, a finding that suggests that CyA may reduce the number of activated lymphocytes preferentially at this early stage of treatment. In contrast, the number of epidermal Langerhans cells increased within 1 week and more markedly by 4 weeks. The expression of EGFR on keratinocytes in all layers of the epidermis persisted during CyA treatment, despite resolution of the lesions. These results suggest that, rather than preventing keratinocyte hyperproliferation via interference with the expression of EGFR, the anti-psoriatic effects of CyA may be mediated, at least in part by interference with T cell activation evident within I week of instigation of therapy.