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Roles of interleukin-18 in the regulation of inflammatory responses

IL-18 在炎症反应调节中的作用

基本信息

批准号：
13470040
负责人：
OKAMURA Haruki
金额：
$ 8.38万
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 (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

Interleukin-18(IL-18) has been shown to be involved in the regulatory mechanism for inflammatory responses. We have shown that IL-18 together with IL-12 strongly induce IFN-γ resulting in production of injurious molecule such as TNFα, nitric oxide, and reactive oxigen species, while in the absence of IL-12, it induces anti-inflammatory cytokines such as IL-4, -5, -10 and -13(Ann.Rev.Immunology, 2001). Thus, IL-18 is considered to be involved in both destructive and compensatory reactions in the inflammatory responses. We have tried to further clarify the roles of IL-18 in the regulatory mechanism for inflammatory responses. IL-18, when singly given to mice, markedly reduces number of circulating leucocytes (Clin.Diagn.Lab.Immunol.2002), while continuous administration causes neutrophilia and eosinophilia (Blood, 2001). The combined administration of IL-12 and IL-18 causes injury in multiple organs and this is due to the excessive production of nitric oxide and to the severe damage in the micro vascular system (J.Interferon cytokine res., 2003). However, we have observed that extraordinarily high levels of TNFα is induced in IL-18 deficient mice, and the bleomycin-induced pneumonia and cerulein-induced pancreatitis are much severe in IL-18 KO mice than in wild type mice (in preparation). Thus, IL-18 plays crucial roles in the tissue injury as well as in the regulation of it. However, we have not yet clarified the mechanism for induction of anti-inflammatory, Th2 type cytokines induced by IL-18. We are now seeking for the regulatory cells induced by IL-18.

白细胞介素-18（IL-18）已被证明参与炎症反应的调节机制。我们已经表明，IL-18与IL-12一起强烈诱导IFN-γ，导致有害分子如TNFα、一氧化氮和反应性氧物质的产生，而在不存在IL-12的情况下，它诱导抗炎细胞因子如IL-4、IL-5、IL-10和IL-13（Ann.Rev.Immunology，2001）。因此，IL-18被认为参与炎症反应中的破坏性和代偿性反应。我们试图进一步阐明IL-18在炎症反应调节机制中的作用。当单独给予小鼠时，IL-18显著减少循环白细胞的数量（Clin.Diagn.Lab.Immunol.2002），而连续给药引起嗜酸性粒细胞增多和嗜酸性粒细胞增多（Blood，2001）。IL-12和IL-18的联合施用引起多个器官的损伤，这是由于一氧化氮的过量产生和微血管系统的严重损伤（J.Interferon cytokine res.，2003年）。然而，我们已经观察到在IL-18缺陷小鼠中诱导了非常高水平的TNFα，并且在IL-18 KO小鼠中博莱霉素诱导的肺炎和雨蛙素诱导的胰腺炎比野生型小鼠（制备中）严重得多。因此，IL-18在组织损伤及其调控中起着重要作用，但IL-18诱导抗炎性Th 2型细胞因子的机制尚未阐明。我们正在寻找IL-18诱导的调节细胞。