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

Environ Health Perspect. 2008 Jun;116(6):799-805. doi: 10.1289/ehp.10981.


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.

Keywords: inhaled corticosteroids; innate immune markers; ozone; sputum neutrophils.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Androstadienes / therapeutic use*
  • Anti-Inflammatory Agents / therapeutic use
  • B7-2 Antigen / metabolism
  • CD11b Antigen / metabolism
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Flow Cytometry
  • Fluticasone
  • HLA-DR Antigens / metabolism
  • Humans
  • Inflammation / chemically induced
  • Inflammation / immunology
  • Inflammation / prevention & control*
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Ozone / poisoning*
  • Receptors, IgG / metabolism
  • Sputum / cytology
  • Sputum / drug effects
  • Sputum / immunology


  • Androstadienes
  • Anti-Inflammatory Agents
  • B7-2 Antigen
  • CD11b Antigen
  • HLA-DR Antigens
  • Receptors, IgG
  • Ozone
  • Fluticasone