IL-23 Is Essential for the Development of Elastase-Induced Pulmonary Inflammation and Emphysema

We recently reported that IL-17A plays a critical role in the development of porcine pancreatic elastase(PPE)–induced emphysema. The proliferation of T-helper type 17 (Th17) cells was induced by IL-23. To determine the contribution of IL-23 to the development of pulmonary emphysema, a mouse model of PPE-induced emphysema was used in which responses of IL-23p19–deficient (IL-23−/−) and wild-type (WT) mice were compared. Intratracheal instillationof PPE induced emphysematous changes in the lungs and was associated with increased levels of IL-23 in lung homogenates. Compared with WT mice, IL-23−/− mice developed significantly lower static compliance values and markedly reduced emphysematous changes on histological analyses after PPE instillation. These changes were associated with lower levels of IL-17A and fewer Th17 cells in the lung. The neutrophiliaseen in bronchoalveolar lavagefluid of WT mice was attenuated in IL-23−/− mice, and the reduction was associated with decreased levels of keratinocyte-der...