Published ahead of print on January 23, 2004, doi:10.1164/rccm.200312-1645OC
© 2004 American Thoracic Society
The Effect of Pranlukast on Allergen-induced Bone Marrow Eosinophilopoiesis in Subjects with AsthmaFirestone Institute for Respiratory Health, St. Joseph's Healthcare; and Department of Medicine, McMaster University, Hamilton, Ontario, Canada Correspondence and requests for reprints should be addressed to Paul M. O'Byrne, M.B., F.R.C.P.I., F.R.C.P.(C), Department of Medicine, McMaster University, Health Sciences Centre, Room 3W10, 1200 Main Street West, Hamilton, ON, L8N 3Z5 Canada. E-mail: obyrnep{at}mcmaster.ca We investigated the mechanisms by which leukotriene receptor antagonists decrease airway eosinophil number. In a randomized, double-blind crossover study, we examined the effects of 2 weeks of treatment with pranlukast 300 mg twice a day or placebo on allergen-induced changes in airway eosinophil number and bone marrow eosinophil progenitors in 15 subjects with mild asthma. Pranlukast treatment for 2 weeks decreased mean sputum eosinophil count from 0.15 x 106/g (5.3% of cells) before treatment to 0.02 x 106/g (0.7% of cells) after treatment (p < 0.05), whereas placebo did not. Pranlukast also decreased the eosinophil count (5.6% at 7 hours and 7.5% at 24 hours) (p < 0.05) after allergen inhalation compared with placebo (13.8% at 7 hours and 15.3% at 24 hours). There was a similar trend for sputum cells immunostaining for EG2, eotaxin, interleukin-5, and regulated upon activation, normal T cell expressed and secreted. Pranlukast also significantly attenuated the allergen-induced increase in the number of bone marrow eosinophil/basophil cfu (mean 0.3) at 24 hours compared with placebo (mean 6.2). The proportion of CD34+ cells expressing the eotaxin receptor CC chemokine receptor 3, 24 hours after allergen inhalation, was 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 • allergen • sputum eosinophil • eosinophil progenitor This article has been cited by other articles:
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