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IL-18 deficiency selectively enhances allergen-induced eosinophilia in mice.

IL-18 缺乏选择性地增强小鼠过敏原诱导的嗜酸性粒细胞增多。

基本信息

批准号：
10670567
负责人：
NISHIOKA Yasuhiro
金额：
$ 1.92万
依托单位：
Hyogo College of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670567/
关键词：
Bronchial asthma IL-18 Apoptosis Eosinophil Fas-Ligand

项目摘要

Th2 cytokines are associated with airway inflammation and hyperreactivity in bronchial asthma, and restoration of Th1/Th2 imbalance is a potential avenue for novel therapies. IL-18 is a cytokine secreted by activated macrophages that induces IFN-g production in T1-type cells. We studies a model of allergic asthma in IL-18-deficient mice to investigate the modulatory role of IL-18 on induction and maintenance of Th2 mucosal immunity. In IL-18-deficient mice, levels of eosinophilia and lung damage were significantly higher than in wild-type C57/B6 littermates. Intrapertioneal administration of rIL-18 in deficient mice, reduced these antigen-induced changes to levels seen in wild-type mice, in association with a decrease in IL-4 in bronchoalveolar lavage fluid and lung tissue. However, administration of rIL-18 did not affect IFN-g level and somewhat enhanced the production of IL-5. Notably, reconstitution with rIL-18 increased the numbers of cells staining for Fas ligand (Fas-L) as well as apoptotic cells stained by nick end-labeling in bronchial submucosa infiltrates. These findings indicate that, in vivo, IL-18 not only inhibited antigen-specific Th2 development but also affected apoptosis via Fas/Fas-L interactions. Apparently as a consequence, IL-18 limited the development of local inflammatory response to antigen.

Th2细胞因子与哮喘的气道炎症和高反应性有关，恢复Th1/Th2失衡是新疗法的潜在途径。IL-18是一种由激活的巨噬细胞分泌的细胞因子，可诱导T1细胞产生干扰素-g。我们研究了IL-18缺陷小鼠的过敏性哮喘模型，以探讨IL-18在诱导和维持Th2黏膜免疫中的调节作用。IL-18缺陷小鼠的嗜酸性粒细胞水平和肺损伤显著高于野生型C57/B6小鼠。在缺陷小鼠体内给予rIL-18，可将这些抗原诱导的变化减少到野生型小鼠中的水平，并与支气管肺泡灌洗液和肺组织中IL-4的减少有关。但rIL-18对干扰素-g水平无影响，但对IL-5的产生有一定的促进作用。值得注意的是，重组rIL-18增加了Fas配体(Fas-L)染色的细胞数量以及缺口末端标记的凋亡细胞在支气管粘膜下层浸润物中的数量。这些结果表明，在体内，IL-18不仅抑制抗原特异性Th2细胞的发育，而且通过Fas/Fas-L相互作用影响细胞凋亡。因此，IL-18限制了局部对抗原的炎症反应的发展。