Blocking IL‐23 Signaling Mitigates Cigarette Smoke‐Induced Murine Emphysema

Abstract

ABSTRACTInflammatory cell infiltration is a characteristic feature of COPD and correlates directly with the severity of the disease. Interleukin‐23 (IL‐23) is a pro‐inflammatory cytokine that regulates Th‐17 inflammation, which mediates many pathophysiological events in COPD. The primary goal of this study was to determine the role of IL‐23 as a mediator of key pathologic processes in cigarette smoke‐induced COPD. In this study, we report an increase in IL23 gene expression in the lung biopsies of COPD patients compared to controls and identified a positive correlation between IL23 gene expression and disease severity. In a cigarette smoke‐induced murine emphysema model, the suppression of IL‐23 with a monoclonal blocking antibody reduced the severity of cigarette smoke‐induced murine emphysema. Mechanistically, the suppression of IL‐23 was associated with a reduction in immune cell infiltration, oxidative stress injury, and apoptosis, suggesting a role for IL‐23 as an essential immune mediator of the inflammatory processes in the pathogenesis of CS‐induced emphysema.