Nishimoto Norihiro, Kishimoto Tadamitsu
Laboratory of Immune Regulation in the Graduate School of Frontier Biosciences, Osaka University, Suita City, Japan.
Nat Clin Pract Rheumatol. 2006 Nov;2(11):619-26. doi: 10.1038/ncprheum0338.
Interleukin (IL)-6 is a pleiotropic cytokine that has important roles in the regulation of the immune response, inflammation, and hematopoiesis. Disruption of IL-6 regulation might, however, affect the immune response and consequently induce immune-mediated inflammatory diseases such as rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease, and Crohn's disease. Overproduction of IL-6 also contributes, through its roles as a growth factor or an antiapoptotic factor, to the development of malignant diseases such as multiple myeloma and renal cancer. Progress in the study of IL-6 has increased our understanding of the pathological roles of this cytokine in these diseases and provided key evidence that antagonizing its activities can be used as a therapeutic strategy. The application of molecular biology techniques to design monoclonal antibodies as therapeutic agents has made it possible to regulate the IL-6 signal to successfully treat diseases that have so far proved refractory to conventional therapies. Blocking IL-6 actions by use of a humanized antibody, tocilizumab, which targets the IL-6 receptor, has been proven to be therapeutically effective for rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease and Crohn's disease. In this review, we discuss a paradigm of IL-6 from basic science to clinical use.
白细胞介素（IL）-6是一种多效性细胞因子，在免疫反应、炎症和造血调控中发挥着重要作用。然而，IL-6调节的破坏可能会影响免疫反应，进而引发免疫介导的炎症性疾病，如类风湿性关节炎、系统性幼年特发性关节炎、卡斯特曼病和克罗恩病。IL-6的过度产生还通过其作为生长因子或抗凋亡因子的作用，促进了恶性疾病如多发性骨髓瘤和肾癌的发展。对IL-6的研究进展加深了我们对这种细胞因子在这些疾病中病理作用的理解，并提供了关键证据，表明拮抗其活性可作为一种治疗策略。应用分子生物学技术设计单克隆抗体作为治疗药物，使得调节IL-6信号以成功治疗迄今对传统疗法难治的疾病成为可能。使用靶向IL-6受体的人源化抗体托珠单抗阻断IL-6的作用，已被证明对类风湿性关节炎、系统性幼年特发性关节炎、卡斯特曼病和克罗恩病具有治疗效果。在本综述中，我们讨论了从基础科学到临床应用的IL-6范例。
