University of Kiel, Biochemistry, Olshausenstrasse 40, Kiel 24098, Germany.
Oregon Health and Science University, GH104, Division of Infectious Diseases, Public Health and Preventive Medicine, 3375 SW Terwilliger Boulevard, Portland, Oregon 97239, USA.
Nat Rev Rheumatol. 2017 Jul;13(7):399-409. doi: 10.1038/nrrheum.2017.83. Epub 2017 Jun 15.
IL-6 is a pleiotropic cytokine with broad-ranging effects within the integrated immune response. One of the roles of IL-6 is to support immunocompetence, defined as the ability of a host to respond to infections. Understanding the precise role of this cytokine in immunocompetence requires a critical appraisal of data derived from both preclinical and clinical studies. Primary immunodeficiency diseases involving IL-6 or its signalling pathways reveal that IL-6 is critical in the defence against numerous types of pathogens. Studies of IL-6 signalling in preclinical models reveal that selective inhibition of either classic IL-6 signalling or IL-6 trans-signalling has differential effects on the host response to different types of infections. Knowledge of such variation might inform bioengineering of new IL-6-targeting molecules and potentially enable modulation of their toxicity. Clinical studies of IL-6 inhibitors, mainly tocilizumab, reveal that their use is associated with an increased rate of both serious and opportunistic infections generally in the range observed with other non-IL-6 directed biologic therapies. Targeting IL-6 has several other important clinical implications related to diagnosis, management and prevention of infectious diseases.
白细胞介素 6（IL-6）是一种具有广泛作用的多功能细胞因子，在综合免疫反应中发挥作用。IL-6 的作用之一是支持免疫能力，即宿主对感染的反应能力。要了解这种细胞因子在免疫能力中的精确作用，需要对临床前和临床研究中得出的数据进行批判性评估。涉及 IL-6 或其信号通路的原发性免疫缺陷疾病表明，IL-6 在防御多种类型的病原体方面至关重要。临床前模型中 IL-6 信号转导的研究表明，经典 IL-6 信号转导或 IL-6 转导信号的选择性抑制对宿主对不同类型感染的反应有不同的影响。了解这种差异可能为新型 IL-6 靶向分子的生物工程提供信息，并有可能调节其毒性。白细胞介素 6 抑制剂（主要是托珠单抗）的临床研究表明，其使用与严重和机会性感染的发生率增加有关，通常与其他非白细胞介素 6 导向的生物治疗观察到的范围一致。靶向 IL-6 还有其他几个与传染病的诊断、管理和预防相关的重要临床意义。
