Division of Rheumatology, University Hospitals of Geneva & Department of Pathology-Immunology, University of Geneva School of Medicine, 26 avenue Beau-Séjour, 1211 Geneva 14, Switzerland.
Nat Rev Rheumatol. 2011 Jun;7(6):321-9. doi: 10.1038/nrrheum.2011.53. Epub 2011 Apr 26.
Interleukin (IL)-33 is a member of the IL-1 family of cytokines. IL-33 is a nuclear protein that is also released into the extracellular space, and thus acts as a dual-function molecule, as does IL-1α. Extracellular IL-33 binds to the cell-surface receptor ST2, leading to the activation of intracellular signaling pathways similar to those used by IL-1. Unlike conventional cytokines, IL-33 might be secreted via unconventional pathways, and can be released upon cell injury as an alarmin. IL-33 is expressed in cells that are in contact with the environment, and acts as an early inducer of inflammation. Its production is then upregulated in inflamed tissues, thus contributing to the further amplification of inflammatory responses. Studies of IL-33-deficient mice will provide more information on intracellular functions of this cytokine. A large body of evidence supports the pathogenic role of IL-33 in asthma and possibly other inflammatory airway conditions. Furthermore, IL-33 has been shown to be involved in experimental models of arthritis and potentially has a pathogenic role in ulcerative colitis and fibrotic conditions, suggesting that IL-33 antagonists might be of interest for the treatment of asthma, rheumatoid arthritis and ulcerative colitis. However, IL-33 also appears to exert important functions in host defense against pathogens and to display cardioprotective properties, which might have implications for the clinical use of IL-33 blockade.
白细胞介素 (IL)-33 是白细胞介素 1 家族细胞因子的成员。IL-33 是一种核蛋白，也会被释放到细胞外空间，因此它像白细胞介素 1α 一样具有双重功能。细胞外的 IL-33 与细胞表面受体 ST2 结合，导致与白细胞介素 1 使用的类似的细胞内信号通路被激活。与传统细胞因子不同，IL-33 可能通过非传统途径被分泌，并且可以作为警报素在细胞损伤时释放。IL-33 表达于与环境接触的细胞中，作为炎症的早期诱导物发挥作用。其产生随后在炎症组织中被上调，从而有助于炎症反应的进一步放大。对 IL-33 缺陷小鼠的研究将提供更多关于这种细胞因子的细胞内功能的信息。大量证据支持 IL-33 在哮喘及可能其他炎症性气道疾病中的致病作用。此外，IL-33 已被证明参与关节炎的实验模型，并且可能在溃疡性结肠炎和纤维化疾病中具有致病作用，这表明 IL-33 拮抗剂可能对治疗哮喘、类风湿关节炎和溃疡性结肠炎具有潜在的应用价值。然而，IL-33 似乎也在宿主防御病原体和发挥心脏保护特性方面发挥着重要作用，这可能对 IL-33 阻断的临床应用具有影响。
