Antiinflammatory activity of the platelet-activating factor receptor antagonist A-85783.

Accumulating evidence suggests an important role for the lipid mediator, platelet-activating factor (PAF), in cutaneous inflammation. In these studies the antiinflammatory effects of the potent and selective lipophilic PAF receptor antagonist A-85783 topically applied to the ventral ears of male Wistar rats were assessed. Intradermal injections of PAF into rat ears resulted in cutaneous inflammation as assessed by both ear thickness measurements and histological evaluation. Pretreatment of the ears with A-85783 resulted in an inhibition of subsequent PAF-induced inflammation. A-85783 treatment also inhibited phorbol myristic acetate-induced cutaneous inflammation, suggesting that the PAF receptor is involved in the etiology of this experimental dermatitis. These findings demonstrate that epicutaneous A-85783 is an appropriate tool to study the role of the PAF receptor in cutaneous inflammation, and suggest the possible clinical utility of this new class of antiinflammatory agents.