Inhibition of airway remodeling in IL-5-deficient mice

J Clin Invest. 2004 Feb;113(4):551-60. doi: 10.1172/JCI19133.


To determine the role of IL-5 in airway remodeling, IL-5-deficient and WT mice were sensitized to OVA and challenged by repetitive administration of OVA for 3 months. IL-5-deficient mice had significantly less peribronchial fibrosis (total lung collagen content, peribronchial collagens III and V) and significantly less peribronchial smooth muscle (thickness of peribronchial smooth muscle layer, alpha-smooth muscle actin immunostaining) compared with WT mice challenged with OVA. WT mice had a significant increase in the number of peribronchial cells staining positive for major basic protein and TGF-beta. In contrast, IL-5-deficient mice had a significant reduction in the number of peribronchial cells staining positive for major basic protein, which was paralleled by a similar reduction in the number of cells staining positive for TGF-beta, suggesting that eosinophils are a significant source of TGF-beta in the remodeled airway. OVA challenge induced significantly higher levels of airway epithelial alphaVbeta6 integrin expression, as well as significantly higher levels of bioactive lung TGF-beta in WT compared with IL-5-deficient mice. Increased airway epithelial expression of alphaVbeta6 integrin may contribute to the increased activation of latent TGF-beta. These results suggest an important role for IL-5, eosinophils, alphaVbeta6, and TGF-beta in airway remodeling.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Neoplasm / metabolism
  • Bronchial Provocation Tests
  • Bronchoalveolar Lavage Fluid / cytology
  • Eosinophils / immunology
  • Eosinophils / metabolism
  • Humans
  • Integrins / metabolism
  • Interleukin-5 / genetics
  • Interleukin-5 / metabolism*
  • Mice
  • Mice, Knockout
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Pulmonary Fibrosis / immunology*
  • Pulmonary Fibrosis / pathology
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology
  • Respiratory System / anatomy & histology
  • Respiratory System / immunology*
  • Respiratory System / metabolism
  • Respiratory System / pathology
  • Transforming Growth Factor beta / metabolism


  • Antigens, Neoplasm
  • Integrins
  • Interleukin-5
  • Transforming Growth Factor beta
  • integrin alphavbeta6
  • Ovalbumin