INHIBITION OF PLATELET-ACTIVATING FACTOR-INDUCED BRONCHOCONSTRICTION BY THE LEUKOTRIENE-D4 RECEPTOR ANTAGONIST ICI 204,219

We determined whether platelet-activating factor (PAF) caused bronchoconstriction through the release of leukotrienes (LT) by studying the effect of a potent LTD4 receptor antagonist, ICI 204,219, on PAF-induced bronchoconstriction in normal subjects. Eight males (age 20 to 36 yr) were given either 40 mg ICI 204,219 orally or matching placebo on 2 study days separated by 2 wk in a double-blind crossover study. Specific airway conductance (SGaw) was measured after inhalation of nebulized PAF (45 mug). ICI 204,219 caused a significant inhibition of PAF-induced bronchoconstriction as assessed by comparison of the maximum fail in SGaw or of the area under the curve of the time course of SGaw. ICI 204,219 did not inhibit PAF-induced neutropenia. PAF-induced bronchoconstriction is mediated largely by the release of sulfidopeptide leukotrienes in normal men.