IL-9 pathway in asthma: New therapeutic targets for allergic inflammatory disorders

Background: Asthma is a complex heritable inflammatory disorder of the airw ays associated with clinical signs of allergic inflammation and bronchial h yperresponsiveness (BHR), The incidence of asthma continues to rise in indu strialized countries despite advances in the identification of cellular and molecular mediators that are associated with the disease. Because of its i mportance in human health, additional research and alternative therapeutic strategies are justified to create more effective treatments for this debil itating disease. Objective: Studies use recombinant inbred mice to demonstrate that BHR in m ouse models of asthma is associated with a genetic alteration at the IL-9 l ocus, where IL-9 expression in lung is strongly associated with bronchial r esponsiveness. me have investigated the ability of intratracheal instilled IL-9 to induce asthmatic-like responses in naive C57BL/6 (B6) mice, which e xpress very low levels of IL-9, Methods: IL-9 or vehicle was intratracheal instilled in naive B6 mice for 1 0 days. Mice were analyzed for effects on BHR, lung eosinophilia, and serum total IgE levels. Results: Phenotypic effects of B6 mice instilled with IL -9 were increased eosinophils in the bronchoalveolar lavage and significant ly elevated serum total IgE, Moreover, IL-9 was found to induce IL-5R alpha in vivo and in vitro, suggesting a potential mechanism for the novel actio ns described for IL-9 on eosinophils. Conclusion: Increased levels of IL-9 in the airway of naive B6 mice induced lung eosinophilia and serum total IgE levels, which are 2 clinical feature s of asthma. These data support a central role for the IL-9 pathway in the complex pathogenesis of allergic inflammation.