Hydroxychloroquine reduces microglial activity and attenuates experimental autoimmune encephalomyelitis
Hydroxychloroquine reduces microglial activity and attenuates experimental autoimmune encephalomyelitis
复制标题
DOI：
10.1016/j.jns.2015.08.1525
复制
发表时间：
2015-11-15
影响因子：
4.4
通讯作者：
Yong, V. Wee
中科院分区：
文献类型：
--
作者：
Koch, Marcus W.;Zabad, Rana;Yong, V. Wee
背景资料：小胶质细胞活化被认为是所有形式MS的疾病活动的关键病理生理机制。羟氯喹（HCQ）是一种具有免疫调节特性的抗疟药物，广泛用于治疗风湿性疾病。在这一系列的实验中，我们探讨HCQ对人小胶质细胞的体外激活和实验性自身免疫性脑炎（EAE）在vivo.Methods的发展的影响：我们激活人小胶质细胞与脂多糖（LPS），并测量浓度的几个促炎和抗炎细胞因子在未经处理和HCQ预处理的文化。我们研究了HCQ预处理在两个剂量的EAE和脊髓histologics.Results的发展的影响：HCQ预处理减少了促炎（TNF-α，IL-6和IL-12）和抗炎（IL-10和IL-1受体拮抗剂）细胞因子在LPS刺激的人小胶质细胞的生产。HCQ预处理延迟了EAE的发作，并减少了Iba-1阳性的小胶质细胞/巨噬细胞和脱髓鞘的迹象，在脊髓HCQ治疗animals.Conclusion：HCQ治疗减少了人类小胶质细胞在体外的激活，延迟了EAE的发作，并减少了代表性的激活巨噬细胞/小胶质细胞和脱髓鞘在脊髓中的治疗小鼠。HCQ是MS进一步临床研究的合理候选药物。（C）2015 Elsevier B. V.保留所有权利。
Background: Microglial activation is thought to be a key pathophysiological mechanism underlying disease activity in all forms of MS. Hydroxychloroquine (HCQ) is an antimalarial drug with immunomodulatory properties that is widely used in the treatment of rheumatological diseases. In this series of experiments, we explore the effect of HCQ on human microglial activation in vitro and on the development of experimental autoimmune encephalitis (EAE) in vivo.Methods: We activated human microglia with lipopolysaccharide (LPS), and measured concentrations of several pro- and anti-inflammatory cytokines in untreated and HCQ pretreated cultures. We investigated the effect of HCQ pretreatment at two doses on the development of EAE and spinal cord histology.Results: HCQ pretreatment reduced the production of pro-inflammatory (TNF-alpha, IL-6, and IL-12) and anti-inflammatory (IL-10 and IL-1 receptor antagonist) cytokines in LPS-stimulated human microglia. HCQ pretreatment delayed the onset of EAE, and reduced the number of Iba-1 positive microglia/macrophages and signs of demyelination in the spinal cords of HCQ treated animals.Conclusion: HCQ treatment reduces the activation of human microglia in vitro, delays the onset of EAE, and decreases the representation of activated macrophages/microglia and demyelination in the spinal cord of treated mice. HCQ is a plausible candidate for further clinical studies in MS. (C) 2015 Elsevier B.V. All rights reserved.