Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-beta, IL-11, IL-17, and type I and type III collagen expression

J Allergy Clin Immunol. 2003 Jun;111(6):1293-8. doi: 10.1067/mai.2003.1557.


Background: Important features of airway remodeling in asthma include the formation of subepithelial fibrosis and increased deposition of types I and III collagen. TGF-beta, IL-11, and IL-17 are profibrotic cytokines involved in the formation of subepithelial fibrosis and are increased in patients with asthma, particularly in those with severe disease.

Objective: The purpose of this study was to investigate the effect of corticosteroids on the expression of these profibrotic cytokines and on extracellular matrix deposition.

Methods: We used immunocytochemistry to measure the expression of TGF-beta, IL-11, IL-17, and collagen types I and III in the airways of patients with mild asthma (n = 9), patients with moderate-to-severe asthma (n = 10), and control subjects without asthma (n = 6). Baseline bronchial biopsy specimens were obtained in all groups. In addition, repeat biopsies were obtained in the patients with moderate-to-severe asthma after a 2-week course of oral corticosteroids.

Results: TGF-beta expression was significantly higher in all groups with asthma, and it did not decrease after treatment with oral corticosteroids. Levels of IL-11 and IL-17 were increased in patients with moderate-to-severe asthma compared with patients with mild asthma and normal controls (P <.05). The expression of these cytokines decreased with oral corticosteroids in the moderate-to-severe group to levels that were comparable to those seen in the patients with mild asthma and in the normal controls (P <.005). Expression of types I and III collagens was higher in the patients with moderate-to-severe asthma than in the patients with mild asthma and the controls (P <.05; P <.001). Treatment with corticosteroids did not decrease the expression of types I and III collagens.

Conclusions: These results confirm the association of increased levels of TGF-beta, IL-11, IL-17, and types I and III collagens with severe disease and suggest that the failure of cortico-steroids to decrease collagen deposition might be due to persistently elevated TGF-beta expression.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adult
  • Asthma / diagnosis
  • Asthma / drug therapy
  • Asthma / immunology*
  • Asthma / metabolism*
  • Bronchi / immunology
  • Bronchi / metabolism
  • Bronchi / pathology
  • Collagen Type I / immunology
  • Collagen Type I / metabolism
  • Collagen Type III / immunology
  • Collagen Type III / metabolism
  • Cytokines / metabolism*
  • Female
  • Fibrillar Collagens / metabolism*
  • Fibrosis
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / pharmacology*
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunohistochemistry
  • Interleukin-11 / immunology
  • Interleukin-11 / metabolism
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Male
  • Methylprednisolone / administration & dosage
  • Methylprednisolone / pharmacology*
  • Methylprednisolone / therapeutic use
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism


  • Collagen Type I
  • Collagen Type III
  • Cytokines
  • Fibrillar Collagens
  • Glucocorticoids
  • Interleukin-11
  • Interleukin-17
  • Transforming Growth Factor beta
  • Methylprednisolone