Interleukin-11 Receptor Subunit Alpha-1 is Required for Maximal Airway Responsiveness to Methacholine After Acute Exposure to Ozone

Interleukin (IL)-11, a pleiotropic, cationic cytokine, contributes to numerous biological processes, including adipogenesis, hematopoiesis, and inflammation. Asthma, a chronic respiratory disease, is notably characterized by reversible airway obstruction, persistent lung inflammation, and airway hyperresponsiveness (AHR). Nasal insufflation of IL-11 causes AHR in wild-type mice while lung inflammation induced by antigen sensitization and challenge, which mimics features of atopic asthma in humans, is attenuated in mice genetically deficient in IL-11 receptor subunit alpha-1 (IL-11Rα1-deficient mice), a transmembrane receptor that is required along with glycoprotein 130 to transduce IL-11 intracellular signaling. Nevertheless, the contribution of IL-11Rα1 to the manifestation of phenotypic features of non-atopic asthma are not presently known. Thus, based on the aforementioned observations, we hypothesized that genetic deficiency of IL-11Rα1 would attenuate lung inflammation and increases in airway responsiveness following acute inhalation exposure to ozone, a criteria pollutant and non-atopic asthma stimulus.