Effect of immunomodulators on bleomycin-lnduced lung injury

S. Kremer, R. Breuer*, I. S. Lossos, N. Berkman, T. G. Christensen, M. W. Connor, R. H. Goldstein, R. Or

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Background: The role of lymphocytes and their subpopulations in lung fibrosis is as yet unclear. Objective: To define the role of immunomodulation in bleomycin-induced inflammatory fibrotic lung injury, by testing the effect of two known Th 1 inhibitors: linomide and pentoxifylline. Methods: C57BL/6 mice were treated by a single intratracheal instillation of 0.06 mg bleomycin in 0.01 ml saline or saline alone. Treatment groups included: (1) intratracheal bleomycin and daily treatment with linomide or pentoxifylline; (2) intratracheal bleomycin and daily water; (3) intratracheal saline and daily linomide or pentoxifylline; (4) intratracheal saline and daily water. Linomide and pentoxifylline were available per os in the drinking water from 1 day prior to intratracheal instillation. Animals were studied 14 days after intratracheal instillation. Lung injury was evaluated by total and differential cell count in bronchoalveolar lavage fluid, by a semiquantitative morphological index of lung injury and a quantitative image analysis of cellularity, fibrosis fraction and alveolar wall area fraction, and by biochemical analysis of lung hydroxyproline content. Results: Linomide or pentoxifylline did not cause any lung injury in saline-treated control mice. Overt signs of lung injury were apparent in bleomycin-treated mice. These changes were not affected by daily treatment with linomide or pentoxifylline, which were given in the highest tolerable dose. Conclusion: This study does not support the use of linomide or pentoxifylline to prevent or ameliorate lung fibrosis and may suggest that drug-induced differentiation of T lymphocytes into Th1/th2 subpopulations does not affect the evolution of bleomycin-induced lung injury.

Original languageAmerican English
Pages (from-to)455-462
Number of pages8
Issue number5
StatePublished - 1999
Externally publishedYes


  • Bleomycin
  • Linomide
  • Lung
  • Mice
  • Pentoxifylline


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