Lung cytokine production in bleomycin-induced pulmonary fibrosis

Exp Lung Res. Jan-Mar 1992;18(1):29-43. doi: 10.3109/01902149209020649.


In bleomycin-induced pulmonary fibrosis, lung injury is accompanied with inflammation and subsequent fibrosis. In this study, lung mRNA for several cytokines was measured in bleomycin-treated mice to evaluate their roles in lung fibrosis. Significant increases in tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) mRNA were found in lungs of bleomycin-treated responder CBA mice but not in nonresponder BALB/c mice. Increases in responder animals peaked on day 7 after bleomycin administration, and subsequently returned toward control levels. This time course paralleled that for the increase in beta-actin mRNA, but preceded the peak increase in mRNA for collagens I and III. When lung macrophages were analyzed for cytokine secretion, differences were observed between alveolar macrophages and interstitial cells, and between cells from bleomycin-responsive CBA and nonresponsive BALB/c mice. Only alveolar macrophages from CBA mice secreted increased amounts of IL-1. TNF-alpha activity was increased in conditioned media of alveolar and interstitial cells of CBA mice, while only alveolar macrophages of nonresponder BALB/c mice secreted any activity. The kinetics of the increased secretion of TNF-alpha was dissimilar for these different cells. These results are consistent with the conclusion that increased production of TNF-alpha and TGF-beta is an important component of the fibrotic process.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Bleomycin
  • Cell Separation
  • Cytokines / biosynthesis*
  • Cytokines / metabolism
  • Female
  • Interleukin-1 / analysis
  • Interleukin-1 / metabolism
  • Lung / cytology
  • Lung / drug effects
  • Lung / metabolism*
  • Macrophages, Alveolar / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred CBA
  • Molecular Sequence Data
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / metabolism*
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • Interleukin-1
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Bleomycin