PAF antagonism as an approach to the treatment of airway hyperreactivity

Abstract

Platelet-activating factor (PAF) would seem a good candidate for a mediator of airway hyperreactivity. It has been reported to induce a long-lasting, if modest, increase in hyperreactivity in both experimental animals and humans. Evidence (albeit often indirect) suggests increased levels associated with bronchial hyperreactivity or the related "late-phase reaction" of asthma. In experimental animals, specific inhibitors of PAF can suppress both allergen and PAF-induced hyperreactivity as well as the late-phase reaction to allergen. The mechanism by which PAF induces hyperreactivity is unknown, but the potent effects of PAF on the eosinophil, a cell characteristic of the inflammatory processes often associated with asthma and hyperreactivity, may be important. A number of potent and selective PAF antagonists are now available. The crucial test for the hypothesis that PAF has a role in human airway hyperreactivity will be the testing of substances such as these in appropriate double-blind, placebo-controlled clinical trials.