Montelukast inhibits inflammatory responses in small airways of the Guinea-pig

Increased resistance in the small airways is a major contributor of airway obstruction in asthma. The role of leukotrienes (LT) in determining inflammation and obstruction of small size bronchi is not completely understood. Here, we have examined the effect of the cysteinyl-leukotriene (CysLT(1)) receptor antagonist, montelukast, against the bronchoconstriction and inflammatory responses induced by exogenous leukotriene and by allergen challenge in small size (<= 1 mm) Guinea-pig bronchi. Montelukast potently (pA(2) 8.3) inhibited the contraction induced by LTD4 in small bronchi taken from naive Guinea-pigs. Furthermore, montelukast reduced the contraction produced by in vitro ovalbumin (OVA) challenge in small size bronchi from sensitized Guinea-pigs. Montelukast (10 mu g kg(-1)) also blocked plasma protein extravasation and accumulation of inflammatory cells (cosinophils) induced by OVA challenge in small intraparenchymal bronchi of OVA sensitized animals. These findings provide additional evidence that CysLT(1) receptor antagonism reduces allergic reactions that cause contractile and inflammatory responses in Guinea-pig small airways during OVA challenge. If the antibronchospastic and anti-inflammatory actions of the CysLT(1) receptor antagonists observed in the small airways of Guinea-pigs occur also in man these effects may contribute to the beneficial effects of montelukast in asthmatic patients. (C) 2007 Published by Elsevier Ltd.