Gudmundsson G, Monick M M, Hunninghake G W
Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
J Immunol. 1998 Jul 15;161(2):991-9.
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.
过敏性肺炎（HP）是一种由吸入有机抗原引起的肉芽肿性炎症性肺病，最常见的病因是嗜热放线菌。只有少数接触这些抗原的个体发病，这表明宿主因素对HP的发生发展很重要。我们比较了敏感小鼠品系C57BL/6和抗性小鼠品系DBA/2中HP的表达情况。它们每周连续3天暴露于嗜热细菌直丝糖多孢菌（SR）或仅暴露于盐水中，持续3周。接触抗原后，C57BL/6小鼠出现肉芽肿性炎症，肺指数（肺重量）增加，而DBA/2小鼠未出现。经14C标记抗原测定，鼻内接种后，两个品系输送到肺部的抗原量相似。抗原暴露后，两个品系的支气管肺泡细胞总数均有相似增加，但C57BL/6小鼠的淋巴细胞更多。与抗性品系相比，敏感品系中抗原诱导的IL-12和IFN-γ基因表达增加更为显著。如果DBA/2小鼠在接触抗原时接受IL-12增强治疗，则其表现类似于敏感的C57BL/6小鼠。这些发现不仅限于肺部，因为C57BL/6小鼠未受刺激和经SR刺激的脾细胞释放的IL-12均明显多于DBA/2小鼠的细胞。然而，DBA/2小鼠的脾细胞在接触IL-12时产生的IFN-γ比C57BL/6小鼠的细胞更多。这些结果表明，对抗原的IL-12反应可能部分调节HP的表达。
