Authors' Affiliations: Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan.
Cancer Immunol Res. 2014 Apr;2(4):288-94. doi: 10.1158/2326-6066.CIR-14-0022.
Cytokines are soluble mediators, which aid cell-to-cell communication in immune responses, and interleukin-6 (IL-6) is a prototypical cytokine featuring redundant and pleiotropic activity. The complete elucidation of the IL-6-mediated signal transduction system has provided a molecular basis for the characteristic features of cytokines. When tissue damage or inflammation due to infections or injuries occurs, IL-6 synthesis is promptly induced, contributing to the host defense through the stimulation of acute-phase immune reactions and hematopoiesis. The production of IL-6 is terminated when tissue homeostasis is restored. The synthesis of IL-6 is tightly regulated transcriptionally and posttranscriptionally. However, the dysregulated continual synthesis of IL-6 has been implicated in the development of various diseases, including autoimmune and chronic inflammatory diseases and cancers. Clinical trials using the humanized anti-IL-6 receptor monoclonal antibody tocilizumab have demonstrated the efficacy of IL-6 blockade for the treatment of refractory inflammatory diseases, such as rheumatoid arthritis, systemic juvenile idiopathic arthritis, and Castleman disease. Moreover, favorable results from the off-label use of tocilizumab strongly suggest that it may be applicable for the treatment of other refractory immune-mediated diseases, including cancer. Therefore, the mechanisms for the dysregulated synthesis of IL-6 need to be elucidated to understand the pathogenesis of the resultant diseases and to facilitate the development of effective therapeutic strategies.
细胞因子是可溶性介质，有助于免疫反应中的细胞间通讯，白细胞介素 6 (IL-6) 是一种典型的细胞因子，具有冗余和多效性活性。IL-6 介导的信号转导系统的完全阐明为细胞因子的特征提供了分子基础。当由于感染或损伤导致组织损伤或炎症时，IL-6 的合成会迅速被诱导，通过刺激急性期免疫反应和造血来促进宿主防御。当组织稳态恢复时，IL-6 的产生就会终止。IL-6 的合成受到转录和转录后水平的严格调控。然而，IL-6 的失调持续合成与各种疾病的发展有关，包括自身免疫性和慢性炎症性疾病以及癌症。使用人源化抗 IL-6 受体单克隆抗体托珠单抗的临床试验已经证明了 IL-6 阻断在治疗难治性炎症性疾病（如类风湿关节炎、全身幼年特发性关节炎和 Castleman 病）方面的疗效。此外，托珠单抗的非适应证使用的良好结果强烈表明，它可能适用于治疗其他难治性免疫介导的疾病，包括癌症。因此，需要阐明 IL-6 失调合成的机制，以了解相关疾病的发病机制，并促进有效治疗策略的开发。
