Analysis of the dynamic significance of IL-18 in allergic Patients

过敏患者IL-18的动态意义分析

• 批准号: 12670446
• 负责人: YOSHIMOTO Tomohiro
• 金额: $ 2.5万
• 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670446/
• 关键词: アレルギー; IL-18; IgE; caspase-1; アトピー性皮膚; アトピー性皮膚炎

IL-18, an IL-1-like cytokine that requires cleavage with caspase-1 to become actiye, has strong ability to induce IFN-y production from T cells, B cells, NK cells, macrophages and dendritic cells, especially in combination with IL-12.In contrast, without IL-12, IL-18 has capacity to induce IL4 and/or IL-13 secretion from NK cells, basophils and mast cells in vitro. We have shown that in the presence of IL-3, IL-18 causes basophils and mast cells to produce large amounts of IL-4, IL-13 and histamine. We have also revealed that naive CD4+ Tcells cultured with IL-2 and IL-18 for 4 days express CD40L and produce IL-4 and IL-13.for induction of IL-18-induced IL-4 and IL-13 production, we need no antigenic stimulation, such as FceR cross-linkage or TCR engagement. Moreover, IL-18-administered mice or IL-18 transgenic mice which endogenously accumulated IL-18 had high serum IgE and this production is dependent on CD4+ T cells, IL-4 and Stat6.These results taken together indicate that IL18 induce allergic disorders, particularly intrinsic atopic diseases characterized by the absence of particular antigen. We call this IL-18-induced allergic disorder as an innate type allergic response.We also found that injection of ovalbumin-specific TCR transgenic BALB/c mice (DOll.10) with a goat-anti-mouse anti-IgD Ab increases IgE production without Th2 polarization. This anti-IgD-induced IgE production on DOll.10 has been revealed to depend upon the intrinsic IL18 and requires IL-4.Finally, we evaluated the serum IL-18 levels from patients with atopic dermatitis and found that IL-18 levels in the sera from patients with atopic dermatitis were significantly elevated compared to those from healthy volunteers. These results indicate that IL18 may be critically involved in regulation of Th2-independent IgE production

IL-18是一种IL-1样细胞因子，需要caspase-1的切割才能激活，在体外能诱导T细胞、B细胞、NK细胞、巨噬细胞和树突状细胞产生IFN-γ，尤其是与IL-12联合使用时。我们已经表明，在IL-3，IL-18的存在下，导致嗜碱性粒细胞和肥大细胞产生大量的IL-4，IL-13和组胺。我们还发现，与IL-2和IL-18一起培养4天的幼稚CD 4 + T细胞表达CD 40 L并产生IL-4和IL-13。为了诱导IL-18诱导的IL-4和IL-13的产生，我们不需要抗原刺激，例如FceR交联或TCR接合。此外，IL-18给药小鼠或内源性积累IL-18的IL-18转基因小鼠具有高血清IgE，这种产生依赖于CD 4 + T细胞、IL-4和Stat 6。这些结果共同表明IL-18诱导过敏性疾病，特别是以缺乏特定抗原为特征的内源性特应性疾病。我们还发现，用山羊抗小鼠抗IgD Ab注射卵清蛋白特异性TCR转基因BALB/c小鼠（DO11.10）可增加IgE的产生，而不产生Th 2极化。这种抗IgD诱导的IgE在DO11.10上的产生已经被揭示依赖于内在的IL-18并且需要IL-4。最后，我们评估了来自特应性皮炎患者的血清IL-18水平，并且发现来自特应性皮炎患者的血清中的IL-18水平与来自健康志愿者的血清相比显著升高。这些结果表明，IL 18可能在调节Th 2-非依赖性IgE产生中起关键作用

项目成果

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