Effects of cyclosporine on cytokines and cytokine receptors in psoriasis

Abstract

Oral cyclosporine is effective in the treatment of recalcitrant psoriasis. However, the precise mechanism(s) are not fully understood. A possible mode of action may be via down-modulation of proinflammatory cytokines that are increased in psoriatic lesions. This study was designed to monitor the effects of cyclosporine treatment on the expression of cytokines, cytokine receptors, and other markers of inflammation in psoriatic skin. Ten patients with recalcitrant psoriasis were treated with cyclosporine. The in vivo effects of cyclosporine on cytokines and their receptors were studied by the use of cryostat-cut sections and a panel of antibodies. The in vitro effects were studied with flow cytometry of epidermal cell suspensions prepared from psoriatic lesions and control skin. Clinical improvement was noted in all patients after 2 weeks of cyclosporine treatment. The expression of interleukin-1 beta, interleukin-8, CD25(IL-2R), CD36 and E-selectin were significantly decreased, whereas the number of tumor necrosis factor-receptor-positive epidermal cells was significantly increased in psoriatic lesions. Clinical improvement of psoriasis with cyclosporine treatment is accompanied by down modulation of proinflammatory epidermal cytokines and decreased dermal inflammation. Thus besides suppressing cytokine production by the inflammatory infiltrate, the beneficial effect of cyclosporine in psoriasis also depends on the inhibition of the epidermal cytokine network.