Introduction of the interleukin-10 gene into mice inhibited bleomycin-induced lung injury in vivo

Am J Physiol Lung Cell Mol Physiol. 2000 May;278(5):L914-22. doi: 10.1152/ajplung.2000.278.5.L914.

Abstract

Interleukin (IL)-10 has been shown to reduce many inflammatory reactions. We investigated the in vivo effects of IL-10 on a bleomycin-induced lung injury model. Hemagglutinating virus of Japan (HVJ)-liposomes containing a human IL-10 expression vector (hIL10-HVJ) or a balanced salt solution as a control (Cont-HVJ) was intraperitoneally injected into mice on day -3. This was followed by intratracheal instillation of bleomycin (0.8 mg/kg) on day 0. Myeloperoxidase activity of bronchoalveolar lavage fluid and tumor necrosis factor-alpha mRNA expression in bronchoalveolar lavage fluid cells on day 7 and hydroxyproline content of the whole lung on day 21 were inhibited significantly by hIL10-HVJ treatment. However, Cont-HVJ treatment could not suppress any of these parameters. We also examined the in vitro effects of IL-10 on the human lung fibroblast cell line WI-38. IL-10 significantly reduced constitutive and transforming growth factor-beta-stimulated type I collagen mRNA expression. However, IL-10 did not affect the proliferation of WI-38 cells induced by platelet-derived growth factor. These data suggested that exogenous IL-10 may be useful in the treatment of pulmonary fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic
  • Bleomycin
  • Cell Division / drug effects
  • Cells, Cultured
  • Collagen / genetics
  • Fibroblasts / immunology
  • Fibroblasts / pathology
  • Gene Expression / immunology
  • Gene Transfer Techniques*
  • Humans
  • Interleukin-10 / genetics*
  • Interleukin-10 / immunology
  • Mice
  • Mice, Inbred C57BL
  • Platelet-Derived Growth Factor / pharmacology
  • Pneumonia / chemically induced
  • Pneumonia / pathology
  • Pneumonia / prevention & control
  • Pulmonary Fibrosis / chemically induced*
  • Pulmonary Fibrosis / pathology
  • Pulmonary Fibrosis / prevention & control
  • RNA, Messenger / analysis
  • Respirovirus / genetics
  • Specific Pathogen-Free Organisms
  • Transforming Growth Factor beta / genetics
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Antibiotics, Antineoplastic
  • Platelet-Derived Growth Factor
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Bleomycin
  • Interleukin-10
  • Collagen