PAF antagonism as an approach to the treatment of airway hyperreactivity.
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.
Meade
C J
CJ
Department of Pharmacology, Boehringer Ingelheim KG, Ingelheim/Rhein, Germany.
Heuer
H
H
D000485:Allergens; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001381:Azepines / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects; D004224:Diterpenes; D046934:Ginkgolides; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology; D014230:Triazoles / Q000494:pharmacology
D000485:Allergens; D001381:Azepines; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; C045856:ginkgolide B