Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction

J Clin Invest. 1996 Dec 15;98(12):2845-53. doi: 10.1172/JCI119113.


Interleukin-11 is a pleotropic cytokine produced by lung stromal cells in response to respiratory viruses, cytokines, and histamine. To further define its potential effector functions, the Clara cell 10-kD protein promoter was used to express IL-11 and the airways of the resulting transgene mice were characterized. In contrast to transgene (-) littermates, the airways of IL-11 transgene (+) animals manifest nodular peribronchiolar mononuclear cell infiltrates and impressive airways remodeling with subepithelial fibrosis. The inflammatory foci contained large numbers of B220(+) and MHC Class II(+) cells and lesser numbers of CD3(+), CD4(+), and CD8(+) cells. The fibrotic response contained increased amounts of types III and I collagen, increased numbers of alpha smooth muscle actin and desmin-containing cells and a spectrum of stromal elements including fibroblasts, myofibroblasts, and smooth muscle cells. Physiologic evaluation also demonstrated that 2-mo-old transgene (+) mice had increased airways resistance and non-specific airways hyperresponsiveness to methacholine when compared with their transgene (-) littermates. These studies demonstrate that the targeted expression of IL-11 in the mouse airway causes a B and T cell-predominant inflammatory response, airway remodeling with increased types III and I collagen, the local accumulation of fibroblasts, myofibroblasts, and myocytes, and obstructive physiologic dysregulation. IL-11 may play an important role in the inflammatory and fibrotic responses in viral and/or nonviral human airway disorders.

Publication types

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

MeSH terms

  • Airway Obstruction / physiopathology*
  • Airway Resistance
  • Animals
  • Blotting, Northern
  • Blotting, Southern
  • Cloning, Molecular
  • Disease Models, Animal
  • Gene Expression Regulation / genetics*
  • Histocytochemistry
  • Immunohistochemistry
  • Interleukin-11 / genetics
  • Interleukin-11 / pharmacology*
  • Lung / drug effects
  • Lung / metabolism
  • Methacholine Chloride / pharmacology
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron
  • Promoter Regions, Genetic / genetics
  • Proteins / metabolism
  • Pulmonary Fibrosis / genetics
  • Pulmonary Fibrosis / metabolism
  • Uteroglobin*


  • Interleukin-11
  • Proteins
  • SCGB1A1 protein, human
  • Scgb1a1 protein, mouse
  • Methacholine Chloride
  • Uteroglobin