The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders
The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders
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DOI：
10.1111/j.1365-2249.2007.03441.x
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发表时间：
2007-08-01
影响因子：
4.6
通讯作者：
Taylor, J. J.
中科院分区：
文献类型：
--
作者：
Barksby, H. E.;Lea, S. R.;Taylor, J. J.
了解细胞因子的免疫生物学是核心的发展合理的治疗破坏性炎症性疾病，如类风湿性关节炎（RA）和牙周炎。经典的白细胞介素-1（IL-1）家族细胞因子IL-1 α和IL-1 β以及IL-18在炎症中起关键作用。最近，IL-1家族的其他成员已经被鉴定。这些细胞因子包括6种细胞因子，其基因位于2号染色体上的IL-1 α和IL-1 β（IL-1F 5 -10）基因的下游，还有IL-33，它是IL-1 R/Toll样受体（TLR）受体超家族成员ST 2的配体。IL-1F 6、IL-1F 8和IL-1F 9是激动剂，并且沿着它们的受体IL-1 Rrp 2在上皮细胞中高度表达，表明在皮肤和包括口腔的胃肠道（GI）中的免疫防御中的作用。滑膜成纤维细胞和关节软骨细胞也表达IL-1 Rrp 2，并对IL-1F 8产生反应，表明其在RA中可能发挥作用。IL-33与RA和克罗恩病患者的发炎组织中的内皮细胞相关，其中它是调节转录的核因子。IL-33也是一种细胞外细胞因子：它在体外和体内诱导T辅助细胞2（Th 2）细胞因子的表达以及小鼠肺和胃肠道的组织病理学变化。修饰IL-1细胞因子的治疗剂（例如重组IL-1 Ra）已在临床上使用，其他治疗剂处于不同的开发阶段（例如抗IL-18抗体）。这篇综述强调了这些新的IL-1细胞因子的新兴数据，并评估其在破坏性炎症性疾病，如RA和牙周炎的发病机制和治疗中可能发挥的作用。
Understanding cytokine immunobiology is central to the development of rational therapies for destructive inflammatory diseases such as rheumatoid arthritis (RA) and periodontitis. The classical interleukin-1 (IL-1) family cytokines, IL-1 alpha and IL-1 beta, as well as IL-18, play key roles in inflammation. Recently, other members of the IL-1 family have been identified. These include six cytokines whose genes are located downstream of the genes for IL-1 alpha and IL-1 beta on chromosome 2 (IL-1F5-10) and also IL-33, which is the ligand for ST2, a member of the IL-1R/Toll-like receptor (TLR) receptor superfamily. IL-1F6, IL-1F8 and Il-1F9 are agonists and, along with their receptor IL-1Rrp2, are highly expressed in epithelial cells suggesting a role in immune defence in the skin and the gastrointestinal (GI) tract including the mouth. Synovial fibroblasts and articular chondrocytes also express IL-1Rrp2 and respond to IL-1F8, indicating a possible role in RA. IL-33 is associated with endothelial cells in the inflamed tissues of patients with RA and Crohn's disease, where it is a nuclear factor which regulates transcription. IL-33 is also an extracellular cytokine: it induces the expression of T helper 2 (Th2) cytokines in vitro and in vivo as well as histopathological changes in the lungs and GI tract of mice. Therapeutic agents which modify IL-1 cytokines (e.g. recombinant IL-1Ra) have been used clinically and others are at various stages of development (e.g. anti-IL-18 antibodies). This review highlights the emerging data on these novel IL-1 cytokines and assesses their possible role in the pathogenesis and therapy of destructive inflammatory disorders such as RA and periodontitis.