LSC 2011 Abstract: The role of IL-25 in rhinovirus-induced asthma exacerbations

Rhinoviruses (RV) are the major causative factor of asthma exacerbations (AE). While Th2-mediated inflammation is implicated in asthma, it is unknown how the immune response to RV infection interacts with Th2 immunity causing an AE. Epithelial-derived IL-25 is an important regulator of Th2 immunity and plays a role in asthma pathogenesis. We hypothesized that RV infection of the epithelium induces IL-25 production facilitating immunopathogenesis of AE. We measured IL-25 mRNA in mouse models of RV infection and RV-induced exacerbation of allergic airway inflammation [1]. In vitro IL-25 gene induction was also assessed in asthmatic and normal bronchial epithelial cells (BEC) infected with RV and stimulated with IL-4. In vivo and in vitro results demonstrated that RV induced IL-25 mRNA as measured by qPCR. Airway challenge with ovalbumin (OVA) followed by RV infection in sensitised mice exacerbated allergic airway inflammation and coincided with enhanced IL-25 mRNA expression compared with allergen or infection alone. Similarly, RV and IL-4 treatment of BECs resulted in the highest levels of IL-25 mRNA. The novel finding that RV infection induces IL-25 represents a link between antiviral responses and Th2 inflammation identifying a role for IL-25 in RV-induced AE. Allergen/IL-4 treatment enhanced RV-dependant IL-25 expression thus a Th2 environment and virus may result in exacerbated Th2 inflammation mediated by IL-25. Reference: 1Bartlett, N.W., et al. Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation. Nat Med 14, 199-204 (2008).