Methods: Type 2 mediators in nasal tissue and lavage fluid from control and CRS patients were measured by Luminex assay. Human sinonasal epithelial cells and BEAS-2B cells were stimulated with IL-13 in the presence and absence of PPIs. The effects of PPIs on IL-13-induced effects were measured by ELISA, qRT-PCR, and pH imaging.
Results: IL-13, eotaxin-2 and eotaxin-3 were highly elevated in CRSwNP compared to control and were correlated with tissue ECP and radiographic severity. CRS patients taking PPIs had significantly lower tissue eotaxin-2 and eotaxin-3 levels than those not taking PPIs. In vitro, 5 different PPIs and the competitive H+/K+-ATPase inhibitor SCH-28080 all significantly inhibited IL-13-induced eotaxin-3 release by airway epithelial cells. In addition, IL-13-induced eotaxin-3 expression was dependent on the presence of extracellular K+ and associated with a PPI sensitive efflux of H+ions.
Conclusions: IL-13, eotaxin-2, and eotaxin-3 in tissue are potential biomarkers of eosinophilia and severity in CRSwNP. Inhibition of IL-13-induced eotaxin-3 by PPIs may provide therapeutic benefit in CRSwNP via a novel H+/K+-dependent mechanism.