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Effect of montelukast pretreatment on inducible nitric oxide synthase mRNA expression in the lungs of antigen-challenged allergic mice


Kobi Sade, MD, Allergy and Asthma Center, Tel-Aviv Sourasky Medical Center, 6 Weizman Street, Tel-Aviv 64239, Israel.


Background Growing evidence suggests that inducible nitric oxide synthase (iNOS) is the main source of the high output of exhaled nitric oxide (NO) in asthma. Treatment of asthmatic patients with glucocorticoids reduces high levels of exhaled NO mainly by inhibiting the transcription of iNOS. A similar reduction in exhaled NO was recently observed in patients treated with the leukotriene receptor antagonists, but the exact interaction between these drugs and iNOS remains obscure.

Objective The purpose of this study was to evaluate the effect of a leukotriene receptor antagonist, montelukast, on the expression and activity of iNOS in a murine model of allergic asthma.

Methods Twenty-four BALB/c mice were sensitized to OVA and were equally divided into 3 groups (Groups 1–3). Eight additional mice were sham sensitized and served as a negative control group (Group 4). Group 1 received montelukast 1 mg/kg/day in their drinking water, Group 2 received dexamethasone 1 mg/kg/day in their drinking water and Groups 3 and 4 received plain tap water. After 1 week, the animals were challenged by inhalation of OVA and, 3 h later, they were killed and their lung cells were isolated by enzymatic tissue digestion. NO generation was measured by a Griess assay, and iNOS mRNA was studied by RT-PCR.

Results A significant increase in iNOS mRNA expression and in NO generation was evident after allergen challenge compared with the controls. Pretreatment with montelukast mildly decreased NO production without producing a concomitant significant decrease in iNOS mRNA expression.

Conclusion: Unlike pretreatment with glucocorticoids, we failed to find compelling evidence for a major role for montelukast treatment in the modulation of iNOS mRNA in a murine model of acute asthma.