Bleomycin-induced lung fibrosis in IL-4-overexpressing and knockout mice

Gabriel Izbicki, Reuven Or, Thomas G. Christensen, Michael J. Segel, Alan Fine, Ronald H. Goldstein, Raphael Breuer

Research output: Contribution to journalArticlepeer-review

Abstract

The role of IL-4 in the development of lung fibrosis is as yet unclear. Bleomycin (Bleo) or saline (Sal) was injected intratracheally into three groups of C57BL/6J mice: transgenic animals that overexpressed IL-4 (IL-4 TG, n = 14), mice with a targeted knockout mutation of the IL-4 gene (IL-4 KO, n = 11), and wild-type (WT, n = 13) mice. At 14 days, lung fibrosis was evaluated by hydroxyproline measurement and by quantitative image analysis of fibrosis fraction and alveolar wall area fraction. Bronchoalveolar lavage cell counts in all Bleo-treated groups demonstrated an increased percentage of lymphocytes with a corresponding decrease in the percentage of macrophages. Comparing Bleo- to Sal-treated controls within each group of mice showed increases in all lung fibrosis parameters in IL-4 KO and WT, but not in any of the parameters in IL-4 TG mice. The severity of Bleo-induced fibrotic response was decreased in overexpressed IL-4 TG compared with IL-4 KO mice. These data negate a critical profibrotic role for IL-4 in Bleo-induced lung fibrosis.

Original languageEnglish
Pages (from-to)L1110-L1116
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume283
Issue number5 27-5
DOIs
StatePublished - 1 Nov 2002
Externally publishedYes

Keywords

  • C57BL/6J
  • Computer-assisted morphometry
  • Interstitial lung disease
  • Transgenic mice

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