PAF receptor antagonists in the treatment of asthma

Platelet-activating factor (PAF) has attracted much attention as a mediator in the pathophysiology of asthma due to the molecule's ability to induce characteristic features of this disease. These include bronchoconstriction, mucus hypersecretion, vascular leakage and oedema, eosinophil recruitment and bronchial hyperreactivity to airway spasmogens. Based on these observations it has been hypothesised that PAF receptor antagonists may have a beneficial role in future treatment of asthma. Results from experimental animal models of asthma have suggested possible efficacy of several receptor antagonists. Following the encouraging results from these models, the first clinical trials using PAF receptor antagonists have been undertaken. However, results from published trials have been conflicting and somewhat discouraging. A possible role of antagonists cannot be excluded, though, as these trials were performed on subjects with mild, stable asthma, and also more potent and specific receptor antagonists are under development. Larger double-blind, placebo-controlled trials on natural asthma might better delineate the utility of PAF receptor antagonists in asthma treatment. This review attempts to bring the reader up-to-date on results from the use of PAF antagonists in experimental and human asthma.