Interleukin-10 modulates the severity of hypersensitivity pneumonitis in mice.
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.
Gudmundsson
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G
Department of Medicine, University of Iowa College of Medicine, and Veterans Administrations Medical Center, Iowa City, Iowa, USA. gunar-gudmundsson@uiowa.edu
Bosch
A
A
Davidson
B L
BL
Berg
D J
DJ
Hunninghake
G W
GW
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000235:genetics; D018014:Gene Transfer Techniques; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D016930:Saccharopolyspora / Q000276:immunology
D000893:Anti-Inflammatory Agents; D000942:Antigens, Bacterial; D016207:Cytokines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016753:Interleukin-10