Striz Ilja
Department of Clinical and Transplant Immunology, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021 Prague 4, Czech Republic
Clin Sci (Lond). 2017 Aug 10;131(17):2241-2256. doi: 10.1042/CS20170098. Print 2017 Sep 1.
Interleukin 1 (IL-1) family is a group of cytokines with multiple local and systemic effects, which regulates both innate and adaptive immune responses. Generally, most IL-1 family cytokines express prevailing pro-inflammatory activities (IL-1α, IL-1β, IL-18, IL-33, IL-36 α, β, γ), whereas others are anti-inflammatory (IL-1Ra (IL-1 receptor antagonist), IL-36Ra, IL-38, IL-37). In addition to their immunomodulatory roles, some of them are also involved in the physiological modulation of homeostatic processes and directly affect mRNA transcription. IL-1 family cytokines bind to specific receptors composed of a ligand-binding chain and an accessory chain. The pro-inflammatory effects of IL-1 family cytokines are regulated on the level of transcription, enzymatic processing of precursors, release of soluble antagonists, and expression of decoy receptors. Members of the IL-1 family regulate the recruitment and activation of effector cells involved in innate and adaptive immunity, but they are also involved in the pathogenesis of chronic disorders, including inflammatory bowel disease, rheumatoid arthritis, and various autoimmune and autoinflammatory diseases. There are only limited data regarding the role of IL-1 cytokines in transplantation. In recent years, targeted therapeutics affecting IL-1 have been used in multiple clinical studies. In addition to the recombinant IL-1Ra, anakinra (highly effective in autoinflammatory diseases and tested for other chronic diseases), the monoclonal antibodies canakinumab, gevokizumab, and rilonacept (a long-acting IL-1 receptor fusion protein) provide further options to block IL-1 activity. Furthermore, new inhibitors of IL-18 (GSK 1070806, ABT-325, rIL-18BP (IL-18 binding protein)) and IL-33 (CNTO-7160) are presently under clinical studies and other molecules are being developed to target IL-1 family cytokines.
白细胞介素1（IL-1）家族是一组具有多种局部和全身作用的细胞因子，可调节先天性和适应性免疫反应。一般来说，大多数IL-1家族细胞因子表现出主要的促炎活性（IL-1α、IL-1β、IL-18、IL-33、IL-36α、β、γ），而其他一些则具有抗炎作用（IL-1Ra（IL-1受体拮抗剂）、IL-36Ra、IL-38、IL-37）。除了它们的免疫调节作用外，其中一些还参与稳态过程的生理调节，并直接影响mRNA转录。IL-1家族细胞因子与由配体结合链和辅助链组成的特异性受体结合。IL-1家族细胞因子的促炎作用在转录水平、前体的酶促加工、可溶性拮抗剂的释放以及诱饵受体的表达上受到调节。IL-1家族成员调节参与先天性和适应性免疫的效应细胞的募集和激活，但它们也参与慢性疾病的发病机制，包括炎症性肠病、类风湿性关节炎以及各种自身免疫性和自身炎症性疾病。关于IL-1细胞因子在移植中的作用的数据有限。近年来，影响IL-1的靶向治疗已用于多项临床研究。除了重组IL-1Ra、阿那白滞素（在自身炎症性疾病中高效且已在其他慢性疾病中进行测试）外，单克隆抗体卡那单抗、 gevokizumab和rilonacept（一种长效IL-1受体融合蛋白）提供了进一步阻断IL-1活性的选择。此外，IL-18（GSK 1070806、ABT-325、rIL-18BP（IL-18结合蛋白））和IL-33（CNTO-7160）的新型抑制剂目前正在进行临床研究，并且正在开发其他靶向IL-1家族细胞因子的分子。
