Compensatory response of IL-1 gene knockout mice after pulmonary infection with Klebsiella pneumoniae

Compensatory response of IL-1 gene knockout mice after pulmonary infection with Klebsiella pneumoniae
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DOI:
10.1099/jmm.0.45736-0
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发表时间:
2005-01-01
影响因子:
3
通讯作者:
Yamaguchi, K
Yamaguchi, K
中科院分区:
医学3区
文献类型:
--
作者:
Tanabe, M;Matsumoto, T;Yamaguchi, K

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本研究旨在确定白细胞介素 (IL)-1 在针对由肺炎克雷伯菌引起的实验诱导肺炎的炎症反应中的作用。肺部感染肺炎克雷伯菌后,比较IL-1基因敲除(IL-1 KO)小鼠和免疫活性野生型(WT)小鼠的宿主免疫反应。不同条件下肺部感染后IL-1 KO和WT小鼠的存活率以及肺和血液中活菌计数没有显着差异。组织病理学分析显示两组小鼠具有相似的炎症反应。然而,在感染早期,IL-1 KO小鼠匀浆肺中肿瘤坏死因子α(TNF-α)的水平显着高于WT小鼠。为了确定内源性 TNF-α 在 IL-1 KO 小鼠恢复或防御机制中的作用,在感染肺炎克雷伯菌之前用抗 TNF-α mAb 治疗小鼠。结果显示,抗 TNF-α mAb 治疗的 IL-1 KO 小鼠的存活率显着低于 BSA 治疗的 IL-1 KO 小鼠。数据表明,IL-1 KO 小鼠中 TNF-α 的补偿性产生有助于宿主防御肺炎克雷伯菌感染。
This study was designed to determine the role of inteleukin (IL)-1 in the inflammatory response against experimentally induced pneumonia caused by Klebsiella pneumoniae. The host immune responses of IL-1 gene knockout (IL-1 KO) mice and immunocompetent wild-type (WT) mice were compared after pulmonary infection with K pneumoniae. There were no significant differences between the survival rates and viable bacterial counts in lungs and blood of IL-1 KO and WT mice after pulmonary infections under different conditions. Histopathological analysis showed a similar inflammatory response in both groups of mice. However, in the early stage of infection, the level of tumour necrosis factor alpha (TNF-alpha) in homogenized lungs of IL-1 KO mice was significantly higher than in WT mice. To determine the role of endogenous TNF-alpha in the recovery or the defence mechanism in IL-1 KO mice, mice were treated with an anti-TNF-alpha mAb be-fore infection with K pneumoniae. The results revealed a significantly lower survival rate of anti-TNF-alpha mAb-treated IL-1 KO mice than BSA-treated IL-1 KO mice. The data suggest that compensatory production of TNF-alpha in IL-1 KO mice contributes to the host defence against K. pneumoniae infection.