IL-13 is required and sufficient for airway acidification in allergic airway inflammation (141.16)

Abstract

Abstract Clinical studies have shown acidification of airways in asthma. Importantly, studies have suggested that acidification contributes to the pathophysiological process. However, the mechanism of acidification is unclear. We developed a novel method for measuring the acidity of mouse airways and demonstrated that mouse airways are acidified during models of allergic airway inflammation. Our studies determined that airway acidification does not develop in IL-13-deficient mice and that IL-13 delivery alone is sufficient to induce airway acidification. There are multiple ways IL-13 could lead to acidification, including direct effects on epithelial cells or through recruitment of inflammatory cells. We demonstrated a partial role for eosinophils in airway acidification as CCR3 and IL-5-deficient mice had decreased extent of airway acidification in allergen-challenged mice. Furthermore, using dimethyl amiloride, a specific inhibitor of the Na+/H+ exchanger, we demonstrated significant inhibition of airway acidification in allergic airway inflammation, suggesting a role for ion (proton) channels. In summary, our studies demonstrate that mouse airways are acidified during allergic airway inflammation. We also showed that the mechanism of airway acidification in asthma involves IL-13-mediated pathways including eosinophils and proton channels. These results have considerable implications for the development of therapies that target airway acidification.