Reduced eosinophil pro-fibrogenic effect in severe childhood asthma compared to mild disease: an effect of corticosteroids?

Pediatr Pulmonol. 2004 Sep;38(3):222-8. doi: 10.1002/ppul.20067.

Abstract

Eosinophils play an important role in inflammation and probably in airway remodeling in asthma. We previously demonstrated that eosinophils from atopic subjects display pro-fibrogenic properties towards lung fibroblasts partially by preformed transforming growth factor-beta (TGF-beta). We hypothesized that the pro-fibrogenic potential of eosinophils is increased in children with life-threatening asthma (LTA). Six children with atopic LTA clinically well-controlled by inhaled corticosteroids (ICS) and 5 children with atopic mild asthma (MA) treated only with inhaled beta(2)-agonists were investigated. The effects of their peripheral blood eosinophils on fibroblast proliferation and lattice contraction were investigated. In addition, TGF-beta(1) and IL-6 eosinophil content were also evaluated. Unexpectedly, eosinophils from LTA increased fibroblast proliferation (5.4-fold) and gel contraction (1.1-fold) significantly less than those from MA. TGF-beta(1) but not IL-6 eosinophil content in LTA was significantly lower than that in MA (2.7-fold). In vitro, addition of dexamethasone on eosinophils stimulated by mast cells resulted in a marked decrease in their TGF-beta(1) content by 1.6-fold. In conclusion, eosinophils from children with ICS-treated LTA displayed significantly less pro-fibrogenic properties than those from MA treated only with beta(2)-agonists. Our data suggest that the pro-fibrogenic effect of eosinophils might be influenced by treatment with ICS in childhood asthma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / therapeutic use
  • Adolescent
  • Albuterol / analogs & derivatives*
  • Albuterol / therapeutic use
  • Androstadienes / therapeutic use
  • Asthma / drug therapy
  • Asthma / physiopathology*
  • Child
  • Cyclopropanes
  • Dexamethasone / therapeutic use
  • Eosinophils / physiology*
  • Female
  • Fibroblasts / physiology
  • Fluticasone
  • Glucocorticoids / therapeutic use*
  • Humans
  • In Vitro Techniques
  • Male
  • Quinolines / therapeutic use
  • Salmeterol Xinafoate
  • Sulfides

Substances

  • Acetates
  • Androstadienes
  • Cyclopropanes
  • Glucocorticoids
  • Quinolines
  • Sulfides
  • Salmeterol Xinafoate
  • Dexamethasone
  • Fluticasone
  • montelukast
  • Albuterol