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 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.
Department of Medicine, University of Washington, Seattle, Washington, USA.
N R
NR
Henig
M L
ML
Aitken
M C
MC
Liu
A S
AS
Yu
W R
WR
Henderson
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000485:Allergens; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D007275:Injections, Intravenous; D010741:Phospholipases A / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010972:Platelet Activating Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000485:Allergens; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase