TY - JOUR
T1 - Effect of recombinant human platelet-activating factor-acetylhydrolase on allergen-induced asthmatic responses
AU - Henig, Noreen R.
AU - Aitken, Moira L.
AU - Liu, Mark C.
AU - Yu, Albert S.
AU - Henderson, William R.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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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U2 - 10.1164/ajrccm.162.2.9911084
DO - 10.1164/ajrccm.162.2.9911084
M3 - Article
C2 - 10934081
AN - SCOPUS:0033841610
SN - 1073-449X
VL - 162
SP - 523
EP - 527
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 2 I
ER -