Maintenance of Airway Hyperresponsiveness in Chronic Asthma May Be Mediated by Th2-Independent Mechanisms

Abstract

Abstract Rationale CD4+, Th2-mediated inflammation is an important component of airway hyperresponsiveness (AHR) in allergic airway disease. IL-4 and IL-13, the prototypic Th2 cytokines, mediate their effects through a common receptor complex made up of IL-4Rα and IL-13Rα1. In this study, we examined the effects of impaired Th2 signaling on AHR using IL-4Rα −/− mice in a murine model of allergic asthma. Methods IL-4Rα −/− mice and control BALB/c (IL-4Rα +/+ ) mice were sensitized to and challenged with Aspergillus fumigatus . Airway disease was assessed at days 14, 28, 51, and 57 after intratracheal conidia challenge. AHR was evaluated by plethysmography after intravenous methacholine. Whole lung levels of cytokines, chemokines, and immunoglobulins were measured by specific ELISA. Paraffin-embedded lung sections were stained for histology. Bronchoalveolar lavage (BAL) fluid was cytospun for differential cell counts. Results While AHR was significantly reduced in IL-4Rα −/− mice (p Conclusions These results demonstrate that airway hyperresponsiveness and mucus production in allergic asthma can be maintained in the absence of a predominant Th2 signaling pathway, suggesting that Th2-independent mechanisms may arbitrate chronic stages of the disease.