The pathophysiological role of IL-13 in COPD

<bold>Introduction:</bold> IL-13 disrupts epithelial barrier integrity, causes smooth muscle contraction and induces goblet cell hyperplasia in cell culture models. The role that IL-13 plays in COPD pathophysiology is unclear. <bold>Methods:</bold> We compared small airway IL-13 expression in COPD patient’s (n=34) vs smoking controls (n=23) by immunohistochemistry. We also examined the effect of IL-13 exposure (1, 5 and 10ng/ml) on bronchial epithelial function and susceptibility to rhinovirus infection. <bold>Results:</bold> Airway smooth muscle IL-13 expression was significantly higher in COPD compared to controls (p=0.04). There was no difference in epithelial and sub-epithelial expression between groups. There was no relationship between IL-13 expression and mucous plugging. IL-13 exposure caused a concentration dependent reduction in trans-epithelial electrical resistance (TEER) and tight junction gene expression (occludin and claudin 3) with maximal effects at 10ng/ml (all p<0.001). There was no effect on cell viability. During rhinovirus infection (RV-1B and RV-16), IL-13 (10ng/ml) exposure increased IFN-β, IFN-λ, IL-33 and TSLP expression (p<0.05) and increased viral replication compared to infected cells not exposed to IL-13 (p=0.03). <bold>Conclusion:</bold> The pathophysiological role of IL-13 in COPD may include increased small airway smooth muscle contraction and increased susceptibility to viral infections. This may contribute to airflow limitation and increased exacerbations.