Department of Clinical Application of Biologics, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan.
Int J Biol Sci. 2012;8(9):1227-36. doi: 10.7150/ijbs.4666. Epub 2012 Oct 24.
Interleukin (IL)-6, a cytokine featuring redundancy and pleiotropic activity, contributes to host defense against acute environmental stress, while dysregulated persistent IL-6 production has been demonstrated to play a pathological role in various autoimmune and chronic inflammatory diseases. Targeting IL-6 is thus a rational approach to the treatment of these diseases. Indeed, clinical trials of tocilizumab, a humanized anti-IL-6 receptor antibody have verified its efficacy and tolerable safety for patients with rheumatoid arthritis, Castleman's disease and systemic juvenile idiopathic arthritis, resulting in approval of this innovative biologic for treatment of these diseases. Moreover, a considerable number of case reports and pilot studies of off-label use of tocilizumab point to the beneficial effects of tocilizumab for a variety of other phenotypically different autoimmune and chronic inflammatory diseases. Elucidation of the source of IL-6 and of mechanisms through which IL-6 production is dysregulated can thus be expected to lead to clarification of the pathogenesis of various diseases.
白细胞介素 (IL)-6 是一种具有冗余性和多效性活性的细胞因子,有助于宿主抵御急性环境应激,而失调的持续 IL-6 产生已被证明在各种自身免疫和慢性炎症性疾病中发挥病理性作用。因此,靶向 IL-6 是治疗这些疾病的合理方法。事实上,托珠单抗(一种人源化抗 IL-6 受体抗体)的临床试验已经证实了其对类风湿关节炎、Castleman 病和全身幼年特发性关节炎患者的疗效和可耐受安全性,从而批准了这种创新的生物制剂用于治疗这些疾病。此外,大量关于托珠单抗的超适应证使用的病例报告和初步研究表明,托珠单抗对多种其他表型不同的自身免疫和慢性炎症性疾病具有有益的效果。因此,阐明 IL-6 的来源以及 IL-6 产生失调的机制有望阐明各种疾病的发病机制。