Alteration of airway pH by asthma-relevant cytokines

<bold>Introduction:</bold> Airway pH imbalances cause physiological disturbances such as airway hyperreactivity, inflammation, ciliary dysfunction, and worsened host defense. Airway pH is low in asthma and is correlated with asthma severity. IL-4, IL-6, IL-13, and IL-17 are associated with asthma and increases in these cytokines are correlated with asthma severity. We hypothesized that exposing airway epithelial cells to these cytokines would decrease airway epithelial cell pH. We further hypothesized that this decrease would be greater in asthma than in airway epithelial cells from subjects with no known airways disease (Control). <bold>Methods:</bold> Primary human airway epithelial cells (HAECs) from a control subject and one with asthma were grown in an air-liquid interface and incubated with 10 ng/mL IL-4, -6, -13, and -17 for 4 hours. HAECs were loaded with pHrodoRed for 30 minutes and imaged with fluorescence microscopy. Images were analyzed with ImageJ to compare intracellular pH between groups. <bold>Results:</bold> Exposure to IL-4 and IL-6 caused a decrease in intracellular pH in asthma HAECs (Figure, p<0.0001). Similarly, IL-4 decreased pH in control HAECs (Figure, p<0.0001). Additionally, IL-13 decreased airway pH in normal HAECs (Figure, p<0.0001). IL-4 caused a greater decrease in pH in asthma HAECS than control HAECs (p<.001). <bold>Conclusion:</bold> Increases in IL-4, IL-6, IL-13, and IL-17 may contribute to airway acidification observed in asthma. <fig><object-id>erj;64/suppl_68/PA2667/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>