Interleukin-1 and interleukin-1 antagonism.
Interleukin-1 and interleukin-1 antagonism.
复制标题
DOI：
10.1182/blood.v77.8.1627.bloodjournal7781627
复制
发表时间：
1991-04
期刊：
影响因子：
20.3
通讯作者：
C. Dinarello
中科院分区：
文献类型：
--
作者：
C. Dinarello
多肽细胞因子白介素-1 (IL-1) 影响几乎所有组织和器官系统。 IL-1 是促炎细胞因子的原型，因为它诱导多种基因的表达和多种蛋白质的合成，进而诱导急性和慢性炎症变化。 IL-1 也是典型的“警报”细胞因子，因为它会增强多种防御机制，特别是免疫学和血液学反应。大多数关于 IL-1 生物学的研究都是在动物身上进行的，但人类受试者最近注射了重组 IL-1，结果证实了 IL-1 的两个基本特性：既是疾病的介质，又是宿主防御的介质。然而，在任何一种情况下，IL-1 的过度或持续产生都会导致正常宿主功能的衰弱；因此，减少IL-1合成或其作用成为许多疾病的治疗目标。在这篇综述中，描述了 IL-1 的结构、基因表达、合成和分泌。此外，还讨论了两种 IL-1 表面受体、可能的信号转导机制、各种生物活性以及疾病状态下 IL-1 的产生。介绍了 IL-1、肿瘤坏死因子和 IL-6 之间的异同。尽管已经提出了各种用于减少IL-1合成和/或拮抗IL-1作用的药物，但最近克隆的天然存在的IL-1受体拮抗剂(IL-1ra)开辟了新的实验和临床方法。这种IL-1ra能够在没有激动剂作用的情况下阻断动物体内IL-1受体的触发，从而降低了血流动力学休克、致命性败血症、炎症性肠病、实验性关节炎和人类白血病细胞自发增殖等疾病的严重程度。
The polypeptide cytokine interleukin-1 (IL-1) affects nearly every tissue and organ system. IL-1 is the prototype of the pro-inflammatory cytokines in that it induces the expression of a variety of genes and the synthesis of several proteins that, in turn, induce acute and chronic inflammatory changes. IL-1 is also the prototypic "alarm" cytokine in that it brings about increases in a variety of defense mechanisms, particularly immunologic and hematologic responses. Most studies on the biology of IL-1 have been performed in animals, but human subjects have recently been injected with recombinant IL-1 and the results confirm the two fundamental properties of IL-1 as being both a mediator of disease as well as of host defense. However, in either situation, over or continued production of IL-1 leads to debilitation of normal host functions; therefore, reduction of IL-1 synthesis or its effects becomes a target of therapy in many diseases. In this review, the structure, gene expression, synthesis, and secretion of IL-1 are described. In addition, the two IL-1 surface receptors, possible signal transduction mechanisms, various biologic activities, and production of IL-1 during disease states are discussed. Similarities and differences between IL-1, tumor necrosis factor, and IL-6 are presented. Although various agents for reducing the synthesis and/or for antagonizing the effects of IL-1 have been proposed, the recent cloning of a naturally occurring IL-1 receptor antagonist (IL-1ra) has opened new experimental and clinical approaches. The ability of this IL-1ra to block the triggering of IL-1 receptors in animals without agonist effects has reduced the severity of diseases such as hemodynamic shock, lethal sepsis, inflammatory bowel disease, experimental arthritis, and the spontaneous proliferation of human leukemic cells.