IL-1 receptor antagonist attenuates proinflammatory responses to rhinovirus in airway epithelium.

Abstract

Rhinoviruses (RVs) are the most common trigger for asthma exacerbations, and there are currently no targeted therapies for viral-induced asthma exacerbations. RV infection causes neutrophilic inflammation, which is often resistant to effects of glucocorticoids. IL-1 receptor antagonist (IL-1RA) treatment reduces neutrophilic inflammation in humans challenged with inhaled endotoxin and thus may have therapeutic potential for RV-induced asthma exacerbations. We sought to test the hypothesis that IL-1RA treatment of airway epithelium reduces RV-mediated proinflammatory cytokine production, which is important for neutrophil recruitment. Human bronchial epithelial cells from deceased donors without prior pulmonary disease were cultured at air-liquid interface and treated with IL-13 to approximate an asthmatic inflammatory milieu. Human bronchial epithelial cells were infected with human RV-16 with or without IL-1RA treatment. RV infection promoted the release of IL-1α and the neutrophil-attractant cytokines IL-6, IL-8, and CXCL10. Proinflammatory cytokine secretion was significantly reduced by IL-1RA treatment without significant change in IFN-β release or RV titer. In addition, IL-1RA reduced MUC5B expression after RV infection without impacting MUC5AC. These data suggest that IL-1RA treatment significantly reduced proinflammatory cytokines while preserving the antiviral response. These results provide evidence for further investigation of IL-1RA as a novel targeted therapy against neutrophil-attractant cytokine release in RV-induced airway inflammatory responses.