IL-13 is associated with reduced illness and replication in primary respiratory syncytial virus infection in the mouse

Zhou, Weisong; Hashimoto, Koichi; Moore, Martin L.; Elias, Jack A.; Zhu, Zhou; Durbin, Joan; Colasurdo, Giuseppe; Rutigliano, John A.; Chiappetta, Constance L.; Goleniewska, Kasia; O’Neal, Jamye F.; Graham, Barney S.; Peebles, R. Stokes

The role of IL-13 in respiratory syncytial virus (RSV) immunopathogenesis is incompletely described. To assess the effect of IL-13 on primary RSV infection, transgenic mice which either overexpress IL-13 in the lung (IL-13 OE) or nontransgenic littermates (IL-13 NT) were challenged intranasally with RSV. IL-13 OE mice had significantly decreased peak viral titers four days after infection compared to non-transgenic littermates. In addition, the IL-13 OE mice had significantly lower RSV-induced weight loss and reduced lung IFN-γ protein expression compared with IL-13 NT mice. In contrast, primary RSV challenge of IL-13 deficient mice resulted in a small, but statistically significant increase in viral titers on day four after infection, no difference in RSV-induced weight loss compared to wild type mice, and augmented IFN-γ production on day 6 after infection. In STAT1-deficient (STAT1 KO) mice, where primary RSV challenge produced high levels of IL-13 production in the lungs, treatment with an IL-13 neutralizing protein resulted in greater peak viral titers both four and six days after RSV and greater RSV-induced weight loss compared to mice treated with a control protein. These results suggest that IL-13 modulates illness from RSV-infection.