Influence of different dosage schedules of inhaled fluticasone propionate on peripheral blood cytokine concentrations in childhood asthma

Clin Exp Allergy. 2002 Oct;32(10):1497-503. doi: 10.1046/j.1365-2745.2002.01512.x.

Abstract

Background: Asthma is characterized by eosinophilic airways inflammation with elevated levels of IL-4, IL-5 and sICAM-1, and reduced levels of IL-10 and IFN-gamma. Inhaled corticosteroids powerfully reduce airways inflammation.

Objective: To investigate if eosinophil counts, serum eosinophilic cationic protein (ECP) and sICAM-1 levels, as well as serum and production of cytokines (IL-4, IL-5, IL-10, IFN-gamma) by peripheral blood monocytes (PBMCs) are useful markers to monitor therapy with inhaled fluticasone propionate (FP) in asthmatic children.

Methods: In a double-blind, 1-year study, 55 asthmatic children (aged 6-10 years) stopped inhaled corticosteroids for a mean period of 24 days and were randomized to receive either FP 200 microg/day (constant dose group), or a starting dose of FP 1000 microg/day with two monthly reductions to 500, 200 and 100 microg/day (stepdown group). Hyper-responsiveness, symptom scores and blood sampling were performed at 2-month intervals.

Results: Symptoms and hyper-responsiveness improved significantly in both treatment groups after reintroduction of FP. Eosinophil counts decreased significantly more during the first 2 months of FP in the stepdown group than in the constant dose group (P = 0.03). We found a trend towards a dose-dependent response in changes of eosinophil counts and serum ECP levels during treatment. Serum IL-4 and IL-5 levels were undetectable in the majority of children. No significant effect of the dose of FP on the release of IL-4, IL-5, IL-10 or IFN-gamma by Con A stimulated PBMCs was found. sICAM-1 levels did not significantly differ at any time point between the two groups.

Conclusion: Serum ECP as well as peripheral blood eosinophils, cytokine production by PBMCs and sICAM-1 levels are insensitive markers in titrating and monitoring therapy with inhaled corticosteroids over a wide dose range in childhood asthma.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Administration, Topical
  • Androstadienes / administration & dosage*
  • Anti-Inflammatory Agents / administration & dosage*
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / physiopathology
  • Biomarkers / blood
  • Blood Proteins / analysis
  • Bronchial Hyperreactivity
  • Cell Adhesion Molecules / blood
  • Child
  • Cytokines / blood*
  • Double-Blind Method
  • Drug Administration Schedule
  • Eosinophil Granule Proteins
  • Eosinophils
  • Female
  • Fluticasone
  • Glucocorticoids
  • Humans
  • Immunoglobulin E / blood
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Interleukin-4 / blood
  • Interleukin-5 / blood
  • Leukocyte Count
  • Male
  • Ribonucleases*

Substances

  • Androstadienes
  • Anti-Inflammatory Agents
  • Biomarkers
  • Blood Proteins
  • Cell Adhesion Molecules
  • Cytokines
  • Eosinophil Granule Proteins
  • Glucocorticoids
  • Interleukin-5
  • Interleukin-10
  • Interleukin-4
  • Immunoglobulin E
  • Interferon-gamma
  • Fluticasone
  • Ribonucleases