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两面性细胞因子白细胞介素 6 在宿主防御和疾病中的作用。

The Two-Faced Cytokine IL-6 in Host Defense and Diseases.

机构信息

Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.

Department of Immunopathology, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.

出版信息

Int J Mol Sci. 2018 Nov 9;19(11):3528. doi: 10.3390/ijms19113528.

Abstract

Interleukein-6 (IL-6), is produced locally from infectious or injured lesions and is delivered to the whole body via the blood stream, promptly activating the host defense system to perform diverse functions. However, excessive or sustained production of IL-6 is involved in various diseases. In diseases, the IL-6 inhibitory strategy begins with the development of the anti-IL-6 receptor antibody, tocilizumab (TCZ). This antibody has shown remarkable effects on Castleman disease, rheumatoid arthritis and juvenile idiopathic arthritis. In 2017, TCZ was proven to work effectively against giant cell arteritis, Takayasu arteritis and cytokine releasing syndrome, initiating a new era for the treatment of these diseases. In this study, the defensive functions of IL-6 and various pathological conditions are compared. Further, the diseases of which TCZ has been approved for treatment are summarized, the updated results of increasing off-label use of TCZ for various diseases are reviewed and the conditions for which IL-6 inhibition might have a beneficial role are discussed. Given the involvement of IL-6 in many pathologies, the diseases that can be improved by IL-6 inhibition will expand. However, the important role of IL-6 in host defense should always be kept in mind in clinical practice.

摘要

白细胞介素-6 (IL-6) 由感染或受伤的病灶局部产生,并通过血液输送到全身,迅速激活宿主防御系统以执行多种功能。然而,IL-6 的过度或持续产生与各种疾病有关。在疾病中,IL-6 的抑制策略始于开发抗 IL-6 受体抗体,托珠单抗(TCZ)。这种抗体已在卡斯特曼病、类风湿关节炎和青少年特发性关节炎中显示出显著效果。2017 年,TCZ 被证明对巨细胞动脉炎、Takayasu 动脉炎和细胞因子释放综合征有效,为这些疾病的治疗开辟了一个新时代。在这项研究中,比较了 IL-6 的防御功能和各种病理状况。此外,总结了 TCZ 已获准治疗的疾病,回顾了 TCZ 用于各种疾病的标签外使用增加的最新结果,并讨论了 IL-6 抑制可能具有有益作用的情况。鉴于 IL-6 参与许多病理过程,IL-6 抑制可改善的疾病将增加。然而,在临床实践中应始终牢记 IL-6 在宿主防御中的重要作用。

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