Published ahead of print on January 23, 2004, doi:10.1164/rccm.200312-1645OC Am. J. Respir. Crit. Care Med., Volume 169, Number 8, April 2004, 915-920 A more recent version of this article appeared on April 15, 2004
Submitted on December 4, 2003 The Effect of Pranlukast on Allergen-Induced Bone Marrow Eosinophilopoeisis in Asthmatic SubjectsKrishnan Parameswaran1,1 Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, Ontario, Canada; Medicine, McMaster University, Hamilton, Ontario, Canada * To whom correspondence should be addressed. E-mail: obyrnep{at}mcmaster.ca.
We investigated the mechanisms by which leukotriene receptor antagonists decrease airway eosinophil number. In a randomized, double blind, cross-over study, we examined the effects of two weeks of treatment with pranlukast 300 mg b.i.d. or placebo on allergen-induced changes in airway eosinophil number and bone marrow eosinophil progenitors in 15 subjects with mild asthma. Pranlukast treatment for two weeks decreased mean sputum eosinophil count from 0.15x106/g (5.3% of cells) before treatment to 0.02x106/g (0.7% of cells) after treatment (p<0.05), while placebo did not. Pranlukast also decreased the eosinophil count (5.6% at 7h and 7.5% at 24h) (p<0.05) after allergen inhalation compared to placebo (13.8% at 7h and 15.3% at 24h). There was similar trend for sputum cells immunostaining for EG2, eotaxin, IL-5 and RANTES. Pranlukast also significantly attenuated the allergen-induced increase in the number of bone marrow eosinophil/basophil colony forming units (mean 0.3) at 24h compared to placebo (mean 6.2). The proportion of CD34+ cells expressing the eotaxin receptor CCR3, 24h after allergen inhalation, were also reduced by pranlukast. We conclude that, the cysteinyl leukotriene receptor antagonist, pranlukast, attenuates allergen-induced increase in airway eosinophils by decreasing bone marrow eosinophilopoiesis and airway chemotactic and eosinophilopoietic cytokines. Key words: leukotriene receptor antagonist, pranlukast, asthma, allergen challenge, sputum eosinophil
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