Dinarello C A
Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA.
Eur Cytokine Netw. 1994 Nov-Dec;5(6):517-31.
Interleukin-1 (IL-1) is primarily an inflammatory cytokine. Biologically, IL-1 is more closely related to tumor necrosis factor (TNF) than any other cytokine or interleukin, although the structure and receptors for IL-1 and TNF are clearly distinct. IL-1 is active in the low pM and fM range and IL-1 receptors (IL-1R) are expressed in most cells, although less than 100 receptors per cell is not an uncommon finding. Based on short-term blockade of IL-1 receptors in humans and animals and IL-1 beta knock-out mice, there is no evidence that IL-1 beta plays a role in development, or normal homeostasis such as metabolism, hematopoiesis, renal and hepatic function or regulation of blood pressure. On the other hand, IL-1 alpha is found constitutively produced by various epithelial cells, keratinocytes of the skin and in the brain. In these locations, IL-1 may contribute to cell growth and repair functions. During inflammation, injury, immunological challenge or infection, IL-1 is produced and because of its multiple biological properties, IL-1 must contribute to disease. Most studies on IL-1 are derived from experiments in which humans or animals are injected with IL-1 or IL-1 is added to cells in vitro. The biological properties of IL-1 suggest that its effects often mimic host responses to infection, inflammation, injury or immunologic challenge. Using specific IL-1 blockade, it is clear IL-1 is playing a critical role in some disease processes. This review will focus on IL-1 as a cytokine of primary and strategic importance to the initiation and progression of inflammatory and infectious diseases.
白细胞介素-1(IL-1)主要是一种炎性细胞因子。从生物学角度来看,IL-1与肿瘤坏死因子(TNF)的关系比任何其他细胞因子或白细胞介素都更为密切,尽管IL-1和TNF的结构及受体明显不同。IL-1在低皮摩尔(pM)和飞摩尔(fM)范围内具有活性,并且IL-1受体(IL-1R)在大多数细胞中都有表达,不过每个细胞中少于100个受体的情况并不罕见。基于对人类和动物的IL-1受体进行短期阻断以及对IL-1β基因敲除小鼠的研究,没有证据表明IL-1β在发育过程或诸如代谢、造血、肾和肝功能或血压调节等正常体内平衡中发挥作用。另一方面,发现IL-1α由各种上皮细胞、皮肤角质形成细胞以及大脑组成性产生。在这些部位,IL-1可能有助于细胞生长和修复功能。在炎症、损伤、免疫挑战或感染期间,IL-1会产生,并且由于其多种生物学特性,IL-1必定会导致疾病。大多数关于IL-1的研究都来自于向人类或动物注射IL-1或在体外将IL-1添加到细胞中的实验。IL-1的生物学特性表明其作用常常模拟宿主对感染、炎症、损伤或免疫挑战的反应。使用特异性的IL-1阻断方法可以明确,IL-1在某些疾病过程中起着关键作用。本综述将聚焦于IL-1作为一种对炎症性和感染性疾病的起始和进展具有首要和战略重要性的细胞因子。