Interleukin-10 modulates the severity of hypersensitivity pneumonitis in mice
Interleukin-10 modulates the severity of hypersensitivity pneumonitis in mice
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DOI：
10.1165/ajrcmb.19.5.3153
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发表时间：
1998-11-01
影响因子：
6.4
通讯作者：
Hunninghake, GW
中科院分区：
文献类型：
--
作者：
Gudmundsson, G;Bosch, A;Hunninghake, GW
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）是必不可少的炎症和肉芽肿形成的HP。白细胞介素-10（IL-10）抵消IFN-γ的许多生物学作用，表明IL-10调节HP中的炎症和肉芽肿形成。我们比较了缺乏IL-10（IL-10敲除[KO]）的C57 BL/6小鼠与野生型（WT）同窝小鼠中HP的表达。将LL-10 KO和WT小鼠暴露于嗜热细菌直枝多孢菌或单独暴露于盐水3周。IL-10基因敲除小鼠的支气管肺泡灌洗液中的细胞计数（2.85 +/- 0.43 × 10（6））高于野生型小鼠（1.4 +/- 0.3 × 10（6）/ml：P < 0.03），中性粒细胞反应更显著。它们在抗原暴露后的炎症也比WT小鼠更大（P < 0.0001）。在IL-10 KO小鼠的肺中，IFN-γ、IL-1和肿瘤坏死因子-α（TNF-α）mRNA的上调增加。腺病毒介导的IL-10基因转移到IL-10 KO小鼠的肝脏中减少了WT小鼠中观察到的炎症。这些研究表明，IL-10在HP中具有重要的抗炎特性，并且缺乏这种细胞因子导致更严重的肉芽肿性炎症反应。
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 die 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. LL-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.