Interleukin 1 and interleukin 18 as mediators of inflammation and the aging process.
Interleukin 1 and interleukin 18 as mediators of inflammation and the aging process.
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DOI：
10.1093/ajcn/83.2.447s
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发表时间：
2006-02
期刊：
影响因子：
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通讯作者：
C. Dinarello
中科院分区：
文献类型：
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作者：
C. Dinarello
在这篇评论中，2细胞因子进行了讨论，相对于炎症过程是根本的老化和死亡率。白细胞介素（IL）-1和IL-18是同一结构家族（IL-1家族或IL-F）的成员;目前该家族有9个成员，但除了IL-1 α、IL-1 β和IL-18外，其他成员都是拮抗剂或仍然没有已知的功能。IL-1 α是一种细胞内细胞因子，具有细胞因子和转录因子的特性。IL-1 β和IL-18密切相关;两者都具有相似的三维结构，并且它们各自的前体形式在被细胞内半胱氨酸蛋白酶caspase-1切割之前是无活性的。NALP 3基因突变的患者，控制caspase-1的活性，容易分泌更多的IL-1 β和IL-18，并患有全身性炎症性疾病。该基因缺陷的患者具有高循环浓度的IL-6、血清淀粉样蛋白A和C-反应蛋白，在阻断IL-1受体后，它们中的每一个都迅速降低，这表明IL-1 β有助于这些衰老炎症机制标志物的升高。动物研究支持IL-1 β和IL-18参与动脉粥样硬化发病机制的概念。例如，IL-18结合蛋白（一种天然存在的IL-18特异性抑制剂）的过表达可防止载脂蛋白E缺陷小鼠中动脉粥样硬化的自发发展。从人类和动物研究中，可以得出结论，IL-1 β和IL-18参与了在衰老过程中增加的基本炎症过程。
In this review, 2 cytokines are discussed with respect to the inflammatory processes that are fundamental to aging and mortality. Both interleukin (IL)-1 and IL-18 are members of the same structural family (IL-1 family, or IL-F); there are presently 9 members of this family, but with the exception of IL-1alpha, IL-1beta, and IL-18, the others are antagonists or remain without known function. IL-1alpha is an intracellular cytokine with properties of both a cytokine and a transcription factor. IL-1beta and IL-18 are closely related; both possess a similar three-dimensional structure, and their respective precursor forms are inactive until cleaved by the intracellular cysteine protease caspase-1. Patients with mutations in the NALP3 gene, which controls the activity of caspase-1, readily secrete more IL-1beta and IL-18 and suffer from systemic inflammatory diseases. Patients with defects in this gene have high circulating concentrations of IL-6, serum amyloid A, and C-reactive protein, each of which decrease rapidly upon blockade of the IL-1 receptor, which suggests that IL-1beta contributes to the elevation of these markers of the inflammatory mechanisms of aging. Animal studies support the concept that IL-1beta and IL-18 participate in the pathogenesis of atherosclerosis. For example, overexpression of the IL-18 binding protein, a naturally occurring, specific inhibitor of IL-18, prevents the spontaneous development of atherosclerosis in apolipoprotein E-deficient mice. From human and animal studies, one may conclude that IL-1beta and IL-18 participate in fundamental inflammatory processes that increase during the aging process.