Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Clin Exp Immunol. 2013 Apr;172(1):37-43. doi: 10.1111/cei.12036.
High mobility group box 1 (HMGB1) is an established inflammatory mediator when released from cells. Recent studies have implicated extracellular HMGB1 in the pathogenesis of various autoimmune diseases. The objective of this study was to determine whether HMGB1 could be a therapeutic target for experimental autoimmune encephalomyelitis (EAE). In this study, an anti-HMGB1 monoclonal antibody was injected intraperitoneally into a mouse model of EAE. We also measured serum cytokines levels in EAE and anti-HMGB1 monoclonal antibody-treated EAE. As a result, intraperitoneal injection of an anti-HMGB1 monoclonal antibody ameliorated the clinical and pathological severity of EAE and attenuated interleukin-17 up-regulation in serum. In conclusion, HMGB1 is involved in EAE pathogenesis and could trigger inflammation in the central nervous system. The novel aspect of this study is the demonstration that anti-HMGB1 ameliorates EAE. HMGB1 may be a novel therapeutic strategy for multiple sclerosis.
高迁移率族蛋白 B1（HMGB1）是一种已被证实的细胞释放的炎症介质。最近的研究表明，细胞外 HMGB1 参与了多种自身免疫性疾病的发病机制。本研究旨在确定 HMGB1 是否可以成为实验性自身免疫性脑脊髓炎（EAE）的治疗靶点。在这项研究中，我们向 EAE 小鼠模型腹腔内注射了一种抗 HMGB1 单克隆抗体。我们还测量了 EAE 患者和抗 HMGB1 单克隆抗体治疗的 EAE 患者血清细胞因子水平。结果表明，腹腔内注射抗 HMGB1 单克隆抗体可改善 EAE 的临床和病理严重程度，并减弱血清中白细胞介素-17 的上调。总之，HMGB1 参与了 EAE 的发病机制，并可能引发中枢神经系统炎症。本研究的新颖之处在于证明了抗 HMGB1 可改善 EAE。HMGB1 可能成为多发性硬化症的一种新的治疗策略。
