One of the most severe pathologic responses of RSV infection is associated with overproduction of cytokines and inflammation, leading to mucus hypersecretion. This study investigated the role of IL-25 in the development of RSV-associated immunopathology. IL-25 and its receptor IL-17RB were increased following RSV infection, and IL-25 blockade using neutralizing antibodies reduced RSV-associated pathology, AHR, and type 2 cytokine production. Likewise, IL-17RB-/- mice demonstrated a modified inflammatory response during RSV infection characterized by decreased Th2 and increased Th17 cytokine production. Additionally, the IL-17RB-/- mice demonstrated significantly reduced inflammation and cytokine production in a model of RSV-driven asthma exacerbation. These results indicate that IL-25 regulates the inflammatory response to RSV infection and that its inhibition may enable a reduction in the severity of RSV-associated pulmonary inflammation, including during viral-induced asthma exacerbation.
Keywords: Th2; cytokines; mucus.
© 2014 Society for Leukocyte Biology.