Am. J. Respir. Crit. Care Med., Volume 162, Number 2, August 2000, 523-527

Effect of Recombinant Human Platelet-activating Factor-Acetylhydrolase on Allergen-induced Asthmatic Responses

NOREEN R. HENIG, MOIRA L. AITKEN, MARK C. LIU, ALBERT S. YU, and WILLIAM R. HENDERSON Jr.

Department of Medicine, University of Washington, Seattle, Washington; Department of Medicine, Johns Hopkins University, Baltimore, Maryland; and ICOS Corporation, Bothell, Washington

Platelet-activating factor (PAF) is a potent lipid mediator associated with key features of asthma such as airway constriction, eosinophil infiltration, edema, and mucus accumulation. Regulation of PAF occurs primarily through degradation to biologically inactive lyso-PAF by cellular and secreted PAF-acetylhydrolase (PAF-AH). We evaluated the effect of human recombinant PAF-AH (rPAF-AH) on the dual phase asthmatic response in atopic subjects with mild asthma. Effects on induced sputum cell counts and differentials, eosinophilic cationic protein (ECP), and tryptase were evaluated. Enrolled subjects demonstrated a positive skin test and a dual asthmatic response to allergen inhalation challenge. Fourteen subjects received rPAF-AH (1 mg/kg) or placebo intravenously in a randomized, double blind, placebo-controlled, two-period crossover study. Treatment with rPAF-AH did not significantly reduce either the early- or late-asthmatic response. Sputum eosinophil cell counts were not affected by treatment, but there was a trend toward a reduction in sputum neutrophils. No significant change in sputum ECP and tryptase was observed between rPAF-AH and placebo. Thus, at the dose studied, the unique anti-PAF agent rPAF-AH demonstrated no significant effect on the allergen-induced dual-phase asthmatic response.

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