The effect of pranlukast on allergen-induced bone marrow eosinophilopoiesis in subjects with asthma.
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 10(6)/g (5.3% of cells) before treatment to 0.02 x 10(6)/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.
Parameswaran
Krishnan
K
Firestone Institute for Respiratory Health, St. Joseph's Healthcare, and Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Watson
Richard
R
Gauvreau
Gail M
GM
Sehmi
Roma
R
O'Byrne
Paul M
PM
D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D001249:Asthma / Q000276:immunology*; D001491:Basophils / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects*; D001985:Bronchial Provocation Tests; D002867:Chromones / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004804:Eosinophils / Q000187:drug effects*; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism; D007958:Leukocyte Count; D019891:Leukopoiesis / Q000187:drug effects*; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D008875:Middle Aged; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D013183:Sputum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism
D018952:Antigens, CD34; C515350:CCR3 protein, human; D002867:Chromones; D015848:Interleukin-5; D020024:Leukotriene Antagonists; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; C047681:pranlukast