摘要：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%, respectively. A similar effect was observed on the airway-specific serum biomarker Clara cell protein 16 (CCP16). Furthermore, FP pretreatment 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 O3-induced airway inflammation and immune cell activation.
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