Effect of recombinant human platelet-activating factor-acetylhydrolase on allergen-induced asthmatic responses

Platelet-activating factor (PAF) is a potent lipid mediator associated with key features of asthma such as airway constriction, eosinophil infiltratio n, edema, and mucus accumulation. Regulation of PAF occurs primarily throug h degradation to biologically inactive lyso-PAF by cellular and secreted PA F-acetylhydrolase (PAF-AH). We evaluated the effect of human recombinant PA F-AH (rPAF-AH) on the dual phase asthmatic response in atopic subjects with mild asthma, Effects on induced sputum cell counts and differentials, eosi nophilic cationic protein (ECP), and tryptase were evaluated. Enrolled subj ects demonstrated a positive skin test and a dual asthmatic response to all ergen inhalation challenge. Fourteen subjects received rPAF-AH (1 mg/kg) or placebo intravenously in a randomized, double blind, placebo-controlled, t wo-period crossover study. Treatment with rPAF-AH did not significantly red uce either the early- or late-asthmatic response. Sputum eosinophil cell co unts were not affected by treatment, but there was a trend toward a reducti on in sputum neutrophils. No significant change in sputum ECP and tryptase was observed between rPAF-AH and placebo. Thus, at the dose studied, the un ique anti-PAF agent rPAF-AH demonstrated no significant effect on the aller gen-induced dual-phase asthmatic response.