© 2005 American Thoracic Society
Bradykinin and Tachykinin-induced Leukotriene Release in Airway Virus InfectionsTo the Editor:We read with interest the study by Dr. Bisgaard and colleagues (1) showing that once-daily treatment with montelukast significantly reduced viral-induced asthma exacerbations in 2- to 5-year-old patients with histories of intermittent asthma symptoms. Similarly to what was observed by Bisgaard and coworkers, data from other recent articles (2, 3) suggest that cys-leukotrienes play a role in airway inflammatory diseases following viral infections and support the idea that treatment with antileukotriene drugs could be useful in controlling viral-induced respiratory illness. Notwithstanding, to date the mechanisms by which viral infections contribute to the development of asthma exacerbations and the mechanisms contributing to cys-leukotriene pathway activation in virus-induced airway infection are still debated. A current hypothesis is that virus infection triggers bradykinin and tachykinin generation (4), mediators involved in the pathogenesis of asthma through both bronchoconstrictive and proinflammatory actions. It is believed that both bradykinin and tachykinin exert their biological effects by inducing cys-leukotriene (cys-LT) production. Thus, cys-LT release induced by bradykinin and tachykinins, such as neurokinin A and substance P, could represent a critical step in the cascade of events leading to asthma exacerbations following virus infection. In this regard, an interaction between bradykinin, tachykinins, and cys-LTs has been demonstrated both in an experimental animal model (5) and in humans; in fact we have recently shown an inhibitory effect of montelukast on airway hyperresponsiveness induced by neurokinin A (6) and bradykinin (7). We believe that the capacity of montelukast to protect against bradykinin and tachykinin-induced bronchoconstriction fits well with studies showing a protective effect of montelukast in virus-induced airway illness where an increased generation of bradykinin and tachykinins occurs. Although the mechanisms involved in viral-induced asthma exacerbations need to be determined, release of bradykinin and tachykinin-induced cys-LTs may play a crucial role in airway inflammatory response in this setting. Cys-leukotriene pathway activation has great clinical relevance and may provide a further explanation for the anti-inflammatory activity and therapeutic utility of leukotriene receptor antagonists in reducing cough and respiratory morbidity after virus respiratory infections (1, 3).
University of Catania, Catania, Italy FOOTNOTES Conflict of Interest Statement: N.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; C.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; C.V. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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