Interferon-gamma is necessary for the expression of hypersensitivity pneumonitis
Interferon-gamma is necessary for the expression of hypersensitivity pneumonitis
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DOI：
10.1172/jci119420
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发表时间：
1997-05-15
影响因子：
15.9
通讯作者：
Hunninghake, GW
中科院分区：
文献类型：
--
作者：
Gudmundsson, G;Hunninghake, GW
农民肺疾病是过敏性肺炎（HP）的常见形式，其特征在于肺中的炎症和肉芽肿形成，干扰素-γ对于感染因子引起的肉芽肿性疾病的表达是重要的;然而，这种介质在调节对吸入抗原的肉芽肿反应的表达中的作用尚不清楚。为了评估这一点，我们比较了不表达编码干扰素-γ（GKO）基因的小鼠与其正常同窝出生小鼠（WT）对吸入抗原的反应。将BALB/c背景的GKO和WT小鼠单独暴露于150 μ g嗜热细菌直枝多孢菌或盐水中，每周连续三天，持续3周。暴露于抗原后，WT小鼠发生与肺重量和支气管肺泡灌洗液（BAL）中细胞数量增加相关的显著肉芽肿性炎症。尽管GKO小鼠也表现出肺重量和BAL液中细胞数量的增加，但在类似的抗原暴露后，它们发展出最小的炎症并且没有肉芽肿。为了进一步评估GKO小鼠中缺乏对抗原的应答是否是由于缺乏IFN-γ，我们通过腹膜内注射替换该介质。当给予替换IFN-γ时，GKO小鼠在肺中发展出肉芽肿性炎症，这些研究表明，IFN-γ是必不可少的表达过敏性肺炎。
Farmers lung disease is a common form of hypersensitivity pneumonitis (HP) and is characterized by inflammation and granuloma formation in the lung, Interferon-gamma is important for the expression of granulomatous diseases caused by infectious agents; however, the role this mediator in regulating expression of the granulomatous response to inhaled antigen is not known, To evaluate this, we compared the response to inhaled antigen of mice that do not express the gene coding for interferon-gamma (GKO) with that of their normal littermates (WT). GKO and WT mice on a BALB/c background were exposed to 150 mu g of the thermophilic bacteria Saccharopolyspora rectivirgula or saline alone, for three consecutive days a week, for 3 wk, After exposure to antigen, WT mice developed a marked granulomatous inflammation associated with an increase in lung weight and numbers of cells in bronchoalveolar lavage fluid (BAL). Although GKO mice also exhibited an increase in lung weight and numbers of cells in BAL fluid, they developed minimal inflammation and no granulomas after a similar exposure to antigen, To further evaluate if the lack of a response to antigen in GKO mice was due to lack of IFN-gamma, we replaced this mediator via intraperitoneal injections, When given replacement IFN-gamma, the GKO mice developed granulomatous inflammation in the lung, These studies show that IFN-gamma is essential for the expression of hypersensitivity pneumonitis.