THE EFFECT OF TOPICAL APPLICATION OF THE PLATELET-ACTIVATING FACTOR-ANTAGONIST, RO-24-0238, IN PSORIASIS-VULGARIS - A CLINICAL AND IMMUNOHISTOCHEMICAL STUDY

Platelet-activating factor (PAF) is considered to be one of the most p otent lipid mediators in allergic and inflammatory reactions. Suggesti ons-that PAF is produced by cutaneous cells, and cells infiltrating th e skin from the blood, have been reported. PAF has been identified in allergic cutaneous reactions and also in psoriatic lesions. The biolog ical activity of PAF is thought to be mediated by cell membrane recept ors. Studies revealed that PAF-antagonists can be active in animal mod els of cutaneous inflammation. In humans PAF-antagonists showed minima l therapeutic improvement in studies of antigen-induced cutaneous resp onses in atopic subjects. No data are available on the effects of PAF- antagonists in psoriasis. The objective of this study was to investiga te the effect of a potent PAF-antagonist (Ro 24-0238, 10% solution in diethylene glycol monoethyl ether) in 10 patients with chronic plaque psoriasis, a placebo-controlled double-blind study. Clinical response was evaluated and markers of inflammation, differentiation and prolife ration were studied immunohistochemically on punch biopsies taken from actively treated and placebo-treated lesions, before and after treatm ent.This study demonstrated that a 10% solution of the PAF-antagonist Po 24-0238 was not effective at the clinical or cell biological level after a 4-week treatment period. The most likely explanation for these negative observations is that PAF is not a significant factor in the pathogenesis of psoriasis.