Methotrexate inhibits the human C5a-induced skin response in patients with psoriasis

In this study we examined the effects of intradermal injections of human complement split product C5a in 10 patients with psoriasis in long-term treatment with methotrexate (MTX). The C5a was injected at the end of the weekly MTX cycle just before the intake of the first MTX dose and 3 h after the second of the 3 doses. The C5a-induced skin response was evaluated by measuring the diameter of the wheal and the area of the flare and by erythema index (EI), which was determined objectively by reflectance spectrophotometry. In all patients the skin response was significantly depressed when C5a was injected after MTX intake. The decrease of wheal, flare, and EI averaged 61.6%, 71.1%, and 57.5%, respectively, when all parameters were obtained at maximal skin response. The in vitro chemotaxis of peripheral blood neutrophils and monocytes from the patients toward C5a was markedly inhibited after intake of MTX (p less than 0.01). The skin biopsies obtained after C5a injection before intake of MTX revealed a perivascular inflammatory infiltrate and considerable dermal edema. After MTX intake the number of infiltrating leukocytes and the degree of dermal edema was markedly reduced. This study indicates that MTX is a potent inhibitor of C5a-induced skin inflammation, and that this inhibition may be caused by a direct effect on circulating neutrophils and monocytes. The results obtained in this work support the idea that anti-inflammatory effects of MTX may be partially responsible for its antipsoriatic effect.