Gudmundsson G, Bosch A, Davidson B L, Berg D J, Hunninghake G W
Department of Medicine, University of Iowa College of Medicine, and Veterans Administrations Medical Center, Iowa City, Iowa, USA.
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.
过敏性肺炎（HP）是一种以肉芽肿形成为特征的炎症性肺部疾病。我们最近发现，干扰素-γ（IFN-γ）对于HP中的炎症和肉芽肿形成至关重要。白细胞介素-10（IL-10）可抵消IFN-γ的许多生物学效应，这表明IL-10可调节HP中的炎症和肉芽肿形成。我们比较了缺乏IL-10的C57BL/6小鼠（IL-10基因敲除[KO]）与野生型（WT）同窝小鼠中HP的表达情况。将IL-10 KO小鼠和WT小鼠暴露于嗜热细菌直丝糖多孢菌或仅暴露于盐水中3周。IL-10 KO小鼠支气管肺泡灌洗液中的细胞计数（2.85±0.43×10⁶）高于WT小鼠（1.4±0.3×10⁶/ml；P<0.03），中性粒细胞反应更为明显。与WT小鼠相比，它们在抗原暴露后的炎症反应也更强烈（P<0.0001）。IL-10 KO小鼠肺中IFN-γ、IL-1和肿瘤坏死因子-α（TNF-α）mRNA的上调增加。通过腺病毒介导将IL-10基因转移至IL-10 KO小鼠的肝脏，可减轻其炎症反应，使其炎症程度与WT小鼠相当。这些研究表明，IL-10在HP中具有重要的抗炎特性，缺乏这种细胞因子会导致更严重的肉芽肿性炎症反应。
