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

Th2细胞因子与支气管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是一种由活化的巨噬细胞分泌的细胞因子，可诱导t1型细胞产生IFN-g。我们建立IL-18缺陷小鼠变应性哮喘模型，探讨IL-18在诱导和维持Th2粘膜免疫中的调节作用。在il -18缺陷小鼠中，嗜酸性粒细胞和肺损伤水平显著高于野生型C57/B6幼崽。在缺乏il -18的小鼠腹腔内给予il -18，将这些抗原诱导的变化降低到野生型小鼠的水平，并与支气管肺泡灌洗液和肺组织中IL-4的减少有关。然而，给药il -18不影响IFN-g水平，并在一定程度上提高了IL-5的产生。值得注意的是，rIL-18重建增加了支气管粘膜下层浸润中Fas配体（Fas- l）染色的细胞数量以及缺口末端标记染色的凋亡细胞数量。这些发现表明，在体内，IL-18不仅抑制抗原特异性Th2的发育，还通过Fas/Fas- l相互作用影响细胞凋亡。显然，IL-18限制了局部抗原炎症反应的发展。

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.