Cystic fibrosis (CF) is characterized by an excessive neutrophilic inflammatory response within the airway as a result of defective
cystic fibrosis transmembrane receptor (CFTR) expression and function.
Interleukin-17A induces airway neutrophilia and
mucin production associated with Pseudomonas aeruginosa colonization, which is associated with the pathophysiology of
cystic fibrosis. The objectives of this study were to use the preclinical murine model of
cystic fibrosis lung
infection and
inflammation to investigate the role of
IL-17 in CF lung pathophysiology and explore therapeutic intervention with a focus on
IL-17. Cftr-deficient mice (CF mice) and wild-type mice (WT mice) infected with P. aeruginosa had robust
IL-17 production early in the
infection associated with a persistent elevated inflammatory response. Intratracheal administration of
IL-17 provoked a neutrophilic response in the airways of WT and CF animals which was similar to that observed with P. aeruginosa
infection. The neutralization of
IL-17 prior to
infection significantly improved the outcomes in the CF mice, suggesting that
IL-17 may be a therapeutic target. We demonstrate in this report that the pathophysiological contribution of
IL-17 may be due to the induction of
chemokines from the epithelium which is augmented by a deficiency of Cftr and ongoing
inflammation. These studies demonstrate the in vivo contribution of
IL-17 in
cystic fibrosis lung disease and the therapeutic validity of attenuating
IL-17 activity in
cystic fibrosis.