Effects of a cysteinyl leukotriene receptor antagonist on eosinophil recruitment in experimental allergic rhinitis

SummaryThe cysteinyl leukotrienes (cysLTs) are potent lipid mediators in allergic disease, acting through a receptor (cysLT1‐R) which can be targeted in rhinitis and asthma. We investigated the effects of cysLT1‐R antagonism in experimental allergic rhinitis, focusing on bone marrow eosinophil progenitor responses. BALB/c mice were sensitized, then given daily intranasal ovalbumin for 2 weeks, with montelukast sodium (5 mg/kg or 2·5 mg/kg) or placebo by gavage. Bone marrow eosinophil/basophil colonies were enumerated, and colony cells were morphologically assessed as indices of eosinophil differentiation and maturation. Montelukast treatment resulted in a significant decrease of eosinophils in the nasal mucosa, and in either bone marrow interleukin (IL)‐5‐, but not IL‐3‐, or granulocyte‐macrophage colony‐stimulating factor‐responsive eosinophil/basophil colony‐forming units, and IL‐5‐stimulated eosinophil maturation. These results indicate that cysLT1‐R antagonism in vivo limits both IL‐5‐responsive eosinophilopoiesis, acting at several stages of eosinophil differentiation and maturation. The anti‐allergic effects of cysLT1‐R antagonists are consistent with the concept that cysLTs and IL‐5 act together in the recruitment of eosinophils and eosinophil progenitors from the marrow during upper airway allergic inflammation.

Effects of a cysteinyl leukotriene receptor antagonist on eosinophil recruitment in experimental allergic rhinitis Journal Articles