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

Neil E. Alexis, John C. Lay, Angela Franciska Haczku, Henry Gong, William Linn, Milan J. Hazucha, Brad Harris, Ruth Tal-Singer, David B. Peden

Research output: Contribution to journalArticle

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)799-805
Number of pages7
JournalEnvironmental Health Perspectives
Volume116
Issue number6
DOIs
StatePublished - Jun 2008
Externally publishedYes

Keywords

  • Inhaled corticosteroids
  • Innate immune marker
  • Ozone
  • Spurum neutrophils

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health

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