Fluticasone propionate protects against ozone-induced airways inflammation and modified immune cell activation markers in healthy volunteers

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Abstract

Background: Ozone exposure induces airway neutrophilia and modifies innate immune monocytic cell-surface phenotypes in healthy individuals. High-dose inhaled corticosteroids can reduce O3-induced airway inflammation, but their effect on innate immune activation is unknown. Objectives: We used a human O3 inhalation challenge model to examine the effectiveness of clinically relevant doses of inhaled corticosteroids on airway inflammation and markers of innate immune activation in healthy volunteers. Methods: Seventeen O3-responsive subjects [> 10% increase in the percentage of polymorphonuclear leukocytes.(PMNs) in sputum, PMNs per milligram vs. baseline sputum] received, placebo, or either a single therapeutic dose (0.5 mg) or a high dose (2 mg) of inhaled fluticasone proprionate (FP) 1 hr before a 3-hr O3 challenge (0.25 ppm) on three separate occasions at least 2 weeks apart. Lung function, exhaled nitric oxide, sputum, and systemic biomarkers were assessed 1-5 hr after the O3 challenge. To determine the effect of FP on cellular function, we assessed sputum cells from seven subjects by flow cytometry for cell-surface marker activation. Results: FP had no effect on O3-induced lung function decline. Compared with placebo, 0.5 mg and 2 mg FP reduced O3-induced sputum neutrophilia by 18% and 35%, respectiviely. A similar effect was observed on the airway-specific serum biomarker Clara cell protein 16 (CCP16). Furthermore, FP pretreament significantly reduced O3 induced modification of CD11b, mCD14, CD64, CD16, HLA-DR, and CD86 on sputum monocytes in a dose-dependent manner. Conclusions: This study confirmed and extended data demonstrating the protective effect of FP against O3Y-induced airway inflammation and immune cell activation.

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Alexis, N. E., Lay, J. C., Haczku, A., Gong, H., Linn, W., Hazucha, M. J., … Peden, D. B. (2008). Fluticasone propionate protects against ozone-induced airways inflammation and modified immune cell activation markers in healthy volunteers. Environmental Health Perspectives, 116(6), 799–805. https://doi.org/10.1289/ehp.10981

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