IL-12 modulates expression of hypersensitivity pneumonitis.
IL-12 modulates expression of hypersensitivity pneumonitis.
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DOI：
10.4049/jimmunol.161.2.991
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发表时间：
1998-07
影响因子：
4.4
通讯作者：
Gunnar Gudmundsson;M. Monick;G. Hunninghake
中科院分区：
文献类型：
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作者：
Gunnar Gudmundsson;M. Monick;G. Hunninghake
过敏性肺炎 (HP) 是一种由吸入有机抗原（最常见的是嗜热放线菌）引起的肉芽肿性炎症性肺部疾病。只有少数接触这些抗原的个体会患上疾病，这表明宿主因素对于 HP 的表达很重要。我们比较了敏感品系小鼠 C57BL/6 和耐药品系小鼠 DBA/2 中 HP 的表达。他们每周连续 3 天暴露于嗜热细菌直肠糖多孢菌 (SR) 或单独的盐水中，持续 3 周。暴露于 Ag 后，C57BL/6 小鼠（而非 DBA/2 小鼠）出现肉芽肿性炎症，肺指数（肺重量）增加。根据 14C 标记的 Ag 测定，两种菌株在鼻内安装后输送到肺部的 Ag 量相似。 Ag 暴露后，两者的支气管肺泡细胞总数也有类似的增加，但 C57BL/6 小鼠的淋巴细胞更多。与抗性菌株相比，敏感菌株Ag诱导的IL-12和IFN-γ基因表达显着增加。如果 DBA/2 小鼠在接触 Ag 时接受 IL-12 增强治疗，则它们与敏感的 C57BL/6 小鼠相似。这些发现不仅限于肺，因为 C57BL/6 小鼠的未刺激和 SR 刺激的脾细胞释放的 IL-12 明显多于 DBA/2 小鼠的细胞。然而，当暴露于 IL-12 时，DBA/2 小鼠的脾细胞比 C57BL/6 小鼠的细胞产生更多的 IFN-γ。这些结果表明 IL-12 对 Ag 的反应可能部分调节 HP 的表达。
Hypersensitivity pneumonitis (HP) is a granulomatous, inflammatory lung disease caused by inhalation of organic Ags, most commonly thermophilic actinomycetes. Only a minority of individuals exposed to these Ags develops disease, suggesting that host factors are important for the expression of HP. We compared the expression of HP in a sensitive strain of mice, C57BL/6, and in a resistant strain of mice, DBA/2. They were exposed to the thermophilic bacteria Saccharopolyspora rectivirgula (SR) or to saline alone for 3 consecutive days/week for 3 wk. After exposure to Ag, C57BL/6 mice, but not DBA/2 mice, developed granulomatous inflammation with an increase in lung index (lung weight). Both strains had similar amounts of Ag delivered to the lungs after intranasal installation, as determined with 14C-labeled Ag. Both also had similar increases in total bronchoalveolar cells after Ag exposure, but the C57BL/6 mice had more lymphocytes. Compared with the resistant strain, the sensitive strain had a significantly greater Ag-induced increase in IL-12 and IFN-gamma gene expression. DBA/2 mice resembled sensitive, C57BL/6 mice if they received IL-12 augmentation therapy at the time of Ag exposure. These findings were not limited to lung, since both unstimulated and SR-stimulated spleen cells from C57BL/6 mice released significantly more IL-12 than cells from DBA/2 mice. However, spleen cells from DBA/2 mice made more IFN-gamma when exposed to IL-12, than cells from C57BL/6 mice. These results suggest that the IL-12 response to Ag may modulate in part the expression of HP.