Tanaka Toshio, Narazaki Masashi, Kishimoto Tadamitsu
Department of Clinical Application of Biologics, Osaka University 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.
Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Cold Spring Harb Perspect Biol. 2014 Sep 4;6(10):a016295. doi: 10.1101/cshperspect.a016295.
Interleukin 6 (IL-6), promptly and transiently produced in response to infections and tissue injuries, contributes to host defense through the stimulation of acute phase responses, hematopoiesis, and immune reactions. Although its expression is strictly controlled by transcriptional and posttranscriptional mechanisms, dysregulated continual synthesis of IL-6 plays a pathological effect on chronic inflammation and autoimmunity. For this reason, tocilizumab, a humanized anti-IL-6 receptor antibody was developed. Various clinical trials have since shown the exceptional efficacy of tocilizumab, which resulted in its approval for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Moreover, tocilizumab is expected to be effective for other intractable immune-mediated diseases. In this context, the mechanism for the continual synthesis of IL-6 needs to be elucidated to facilitate the development of more specific therapeutic approaches and analysis of the pathogenesis of specific diseases.
白细胞介素6（IL-6）在感染和组织损伤后迅速短暂产生，通过刺激急性期反应、造血和免疫反应来促进宿主防御。尽管其表达受到转录和转录后机制的严格控制，但IL-6的失调持续合成对慢性炎症和自身免疫产生病理影响。因此，开发了一种人源化抗IL-6受体抗体托珠单抗。此后的各种临床试验表明托珠单抗具有卓越疗效，这使其获批用于治疗类风湿性关节炎和幼年特发性关节炎。此外，托珠单抗有望对其他难治性免疫介导疾病有效。在此背景下，需要阐明IL-6持续合成的机制，以促进更具特异性治疗方法的开发以及特定疾病发病机制的分析。
