Molecular mechanisms in allergy and clinical immunology: IL-11: Insights in asthma from overexpression transgenic modeling

Tao Zheng, Zhou Zhu, Jingming Wang, Robert J. Homer, Jack A. Elias

Research output: Contribution to journalArticlepeer-review

Abstract

The evolution of our understanding of IL-11 mirrors, in many ways, the problems that are faced by investigators in the postgenome era and the types of techniques that might need to be used to deal with these issues. IL-11 was discovered as a soluble factor in fibroblast supernatants that stimulated the proliferation of "IL-6-dependent" plasmacytoma cells. It was subsequently demonstrated to be an important stimulator of platelet reconstitution and a pleiotropic regulator of nonrespiratory tissues. In the lung, IL-11 is produced by a variety of structural cells and eosinophils in response to a variety of stimuli, including TGF-β, major basic proteins, and viruses. IL-11 is also detected in exaggerated quantities at sites of virus infection. Its potential effector functions at these sites were defined with constitutive and inducible overexpression transgenic modeling systems which demonstrated that IL-11 causes nodular mononuclear infiltrates, airway remodeling with subepithelial fibrosis, airways obstruction, and airways hyperresponsiveness and can block alveolar development when expressed during development. In accord with these murine findings, IL-11 is selectively expressed in eosinophils and epithelial cells in patients with moderate and severe asthma where expression correlates directly with disease severity and inversely with FEV1. Studies using transgenic mice also demonstrated that IL-11 inhibits antigen-induced tissue inflammation. Thus IL-11 might be an important regulator of inflammatory and remodeling responses in the asthmatic airway.

Original languageEnglish (US)
Article number71974
Pages (from-to)489-496
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume108
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Airway remodeling
  • Asthma
  • Fibrosis
  • Interleukin 11
  • Transgenic modeling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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