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

  • Author(s): Alexis, Neil E
  • Lay, John C
  • Haczku, Angela
  • Gong, Henry
  • Linn, William
  • Hazucha, Milan J
  • Harris, Brad
  • Tal-Singer, Ruth
  • Peden, David B
  • et al.

Published Web Location

https://doi.org/10.1289/ehp.10981
Abstract

Background

Ozone exposure induces airway neutrophilia and modifies innate immune monocytic cell-surface phenotypes in healthy individuals. High-dose inhaled corticosteroids can reduce O(3)-induced airway inflammation, but their effect on innate immune activation is unknown.

Objectives

We used a human O(3) 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 O(3)-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 O(3) 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 O(3) 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 O(3)-induced lung function decline. Compared with placebo, 0.5 mg and 2 mg FP reduced O(3)-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 O(3)-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 O(3)-induced airway inflammation and immune cell activation.

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