Interleukin-10 modulates the severity of hypersensitivity pneumonitis in mice

Am J Respir Cell Mol Biol. 1998 Nov;19(5):812-8. doi: 10.1165/ajrcmb.19.5.3153.


Hypersensitivity pneumonitis (HP) is an inflammatory lung disease characterized by granuloma formation. We recently showed that interferon-gamma (IFN-gamma) is essential for inflammation and granuloma formation in HP. Interleukin-10 (IL-10) counteracts many of the biologic effects of IFN-gamma, suggesting that IL-10 modulates inflammation and granuloma formation in HP. We compared the expression of HP in C57BL/6 mice that lack IL-10 (IL-10 knockout [KO]) with that in wild-type (WT) littermates. IL-10 KO and WT mice were exposed to the thermophilic bacteria Saccharopolyspora rectivirgula or to saline alone for 3 wk. The IL-10 KO mice had higher cell counts in their bronchoalveolar lavage fluid (2.85 +/- 0. 43 x 10(6)) than did WT mice (1.4 +/- 0.3 x 10(6)/ml; P < 0.03), with a more prominent neutrophil response. They also had greater inflammation after antigen exposure than did the WT mice (P < 0. 0001). There was increased upregulation of IFN-gamma, IL-1, and tumor necrosis factor-alpha (TNF-alpha) mRNAs in the lungs of IL-10 KO mice. Adenovirus-mediated gene transfer of IL-10 to the liver of IL-10 KO mice reduced the inflammation from that seen in WT mice. These studies show that IL-10 has important anti-inflammatory properties in HP, and that lack of this cytokine leads to a more severe granulomatous inflammatory response.

Publication types

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

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Anti-Inflammatory Agents / immunology
  • Antigens, Bacterial / immunology
  • Bronchoalveolar Lavage Fluid / cytology
  • Cytokines / genetics
  • Gene Transfer Techniques
  • Hypersensitivity / immunology*
  • Inflammation / immunology
  • Interleukin-10 / genetics*
  • Interleukin-10 / metabolism
  • Lung / immunology*
  • Lung / pathology
  • Mice
  • Mice, Knockout
  • Pneumonia / immunology*
  • RNA, Messenger / genetics
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Saccharopolyspora / immunology


  • Anti-Inflammatory Agents
  • Antigens, Bacterial
  • Cytokines
  • RNA, Messenger
  • Recombinant Proteins
  • Interleukin-10