Am. J. Respir. Cell Mol. Biol., Volume 19, Number 5, November, 1998 812-818

Interleukin-10 Modulates the Severity of Hypersensitivity Pneumonitis in Mice

Gunnar Gudmundsson, Assumpció Bosch, Beverly L. Davidson, Daniel J. Berg, and Gary W. Hunninghake

Department of Medicine, University of Iowa College of Medicine, and Veterans Administrations Medical Center, Iowa City, Iowa

Hypersensitivity pneumonitis (HP) is an inflammatory lung disease characterized by granuloma formation. We recently showed that interferon- (IFN-) is essential for inflammation and granuloma formation in HP. Interleukin-10 (IL-10) counteracts many of the biologic effects of IFN-, 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 × 10⁶) than did WT mice (1.4 ± 0.3 × 10⁶/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-, IL-1, and tumor necrosis factor- (TNF-) 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.

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