IL-23 is essential to the development of elastase-induced pulmonary inflammation and emphysema

Abstract

RATIONALE: We have recently reported that IL-17A plays a critical role to the development of porcine pancreatic elastase (PPE)-induced emphysema. The proliferation of Th17 cells is induced by IL-23, however, the role of IL-23 in pulmonary emphysema remains uncertain. METHODS: Using a murine model of PPE-induced pulmonary emphysema, we assessed IL-23p19-deficient (IL-23-/-) mice and wild type (WT) mice. Intra-tracheal instillation of PPE induced increased emphysematous change of the lungs on day 21, associated with increased levels of IL-23 in lung homogenates. RESULT: IL-23-/- mice developed significantly lower static compliance values and decreased emphysematous changes in the lung tissue compared to WT mice on day 21 after PPE-instillation, associated with lower levels of IL-17 and lower numbers of Th17 cells in the lung. CONCLUSION: These data identify the important contribution of IL-23 to the development of elastase-induced pulmonary inflammation and emphysema probably through IL-23-IL-17 pathway. Targeting IL-23 in emphysema is a potential therapeutic strategy for delaying disease progression.