Montelukast, a leukotriene receptor antagonist, inhibits the late airway response to antigen, airway eosinophilia, and IL-5-expressing cells in BrownNorway rats

Background: Asthma is characterized by airflow obstruction, inflammatory ce ll infiltration, and the synthesis of mediators, such as T-H2 cytokines and leukotrienes, in the airways. Cysteinyl leukotriene (cysLT) receptor antag onists have recently been associated with clinical improvement of asthma an d reduced airway inflammation. Whether the beneficial effects of cysLT anta gonists are mediated through the modulation of cytokine expression has not been determined, Objective: The aim of the study was to determine the presence of eosinophil s and IL-5 messenger (m)RNA(+) cells within the lungs of antigen-challenged Brown Norway rats after treatment with the cysLT(1) receptor antagonist mo ntelukast (MK). Methods: Ovalbumin-sensitized Brown Norway rats were treated with either MK or saline before ovalbumin challenge, Pulmonary mechanics were monitored f or 8 hours. Subsequently, immunocytochemistry and in situ hybridization wer e used to examine bronchoalveolar lavage (BAL) fluid and lung tissue for ce lls expressing major basic protein (eosinophils) and IL-5 mRNA, respectivel y. Simultaneous in situ hybridization and immunocytochemistry was used to p henotype the cells expressing mRNA encoding IL-5. Results: Animals treated with MK had significantly lower lung resistance an d fewer eosinophils and IL-5 mRNA(+) cells within BAL fluid and lung tissue compared with that found in saline-treated animals. Colocalizaton studies revealed that the majority of IL-5 mRNA(+) cells were T cells and that the number of IL-5 mRNA(+)/CD3(+) or IL-5 mRNA(+)/major basic proteins cells we re significantly less within BAL from animals treated with MK than from tho se treated with saline. Conclusions: These results indicate that the cysLT(1) receptor antagonist M K can diminish the pulmonary response to antigen, tissue eosinophilia, and the number of cells expressing IL-5 mRNA, suggesting that leukotrienes may also regulate the allergic response through the modulation of inflammation and cytokine synthesis.