IL-22 exacerbates weight loss in a murine model of chronic pulmonary Pseudomonas aeruginosa infection

BACKGROUND: Interleukin (IL)-22 is a critical mediator of mucosal immunity and tissue regeneration, protecting against a number of respiratory pathogens. Whether IL-22 confers protection against chronic Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) is unknown. METHODS: Explanted CF lungs were examined for IL-22 production and immune-localization. A murine model of persistent pulmonary PA infection was used to examine production of IL-22 following infective challenge. The role of IL-22 was examined using IL-22 knockout (KO) animals. RESULTS: IL-22 is produced within the adult CF lung and localizes to the airway epithelium. IL-22 is produced by murine pulmonary lymph node cells following lung infection. The absence of IL-22 resulted in no significant difference in acute mortality, bacterial burden, chronic infection rates, histological changes or neutrophilic inflammation in the chronic PA infection model. However, IL-22 KO animals lost less weight following infection. CONCLUSION: IL-22 is produced in the CF lung and in response to PA infection yet is dispensable in protection against chronic pulmonary P. aeruginosa infection in a murine model. However, we identified a novel role for the cytokine in promoting infection-related weight-loss, a significant prognostic factor in the CF population.