The effect of pranlukast on allergen-induced bone marrow eosinophilopoiesis in asthmatic subjects

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 0.15x10 6 /g (5.3% of cells) before treatment to 0.02x10 6 /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. Abstract word count: 195