Quetiapine, an Atypical Antipsychotic, Is Protective against Autoimmune-Mediated Demyelination by Inhibiting Effector T Cell Proliferation
Quetiapine, an Atypical Antipsychotic, Is Protective against Autoimmune-Mediated Demyelination by Inhibiting Effector T Cell Proliferation
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喹硫平是一种非典型抗精神病药，通过抑制效应 T 细胞增殖来预防自身免疫介导的脱髓鞘
DOI：
10.1371/journal.pone.0042746
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发表时间：
2012-08-13
期刊：
影响因子：
3.7
通讯作者：
Xiao, Lan
中科院分区：
文献类型：
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作者：
Mei, Feng;Guo, Sheng;Xiao, Lan
奎替卡松（Quetiopathy，Que）是一种常用的非典型抗精神病药物，能在不引起免疫攻击的情况下阻止髓鞘的破坏。多发性硬化症（MS）是一种自身免疫反应性炎症脱髓鞘疾病，由活化的髓鞘特异性T淋巴细胞（T细胞）触发。在这项研究中，我们研究了Que作为实验性自身免疫性脑脊髓炎（EAE）免疫调节治疗剂的潜在疗效，MS的小鼠模型。在MOG 35 -55肽诱导的EAE小鼠发作时开始Que治疗，并通过流式细胞术分析CD 4 +/CD 8+群体和效应T细胞的增殖来确定Que调节免疫应答的功效（CD4+CD25−）。我们的研究结果表明，Que显着减弱EAE症状的严重程度。Que治疗降低了CD 4 +/CD 8 + T细胞浸润到脊髓中的程度，并抑制了局部神经胶质细胞活化，从而减少了EAE小鼠脊髓中成熟少突胶质细胞的损失和髓磷脂分解。我们的研究结果进一步表明，Que治疗减少了EAE小鼠淋巴结和脾脏中的CD 4 +/CD 8 + T细胞群，并抑制MOG 35 -55或抗CD 3诱导的增殖以及从EAE小鼠脾脏分离的效应T细胞（CD 4 + CD 25 −）的IL-2产生。总之，这些发现表明，Que在EAE过程中显示出免疫调节作用，因此可能是治疗MS的有希望的候选者。
Quetiapine (Que), a commonly used atypical antipsychotic drug (APD), can prevent myelin from breakdown without immune attack. Multiple sclerosisis (MS), an autoimmune reactive inflammation demyelinating disease, is triggered by activated myelin-specific T lymphocytes (T cells). In this study, we investigated the potential efficacy of Que as an immune-modulating therapeutic agent for experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. Que treatment was initiated on the onset of MOG35–55 peptide induced EAE mice and the efficacy of Que on modulating the immune response was determined by Flow Cytometry through analyzing CD4+/CD8+ populations and the proliferation of effector T cells (CD4+CD25−) in peripheral immune organs. Our results show that Que dramatically attenuates the severity of EAE symptoms. Que treatment decreases the extent of CD4+/CD8+ T cell infiltration into the spinal cord and suppresses local glial activation, thereby diminishing the loss of mature oligodendrocytes and myelin breakdown in the spinal cord of EAE mice. Our results further demonstrate that Que treatment decreases the CD4+/CD8+ T cell populations in lymph nodes and spleens of EAE mice and inhibits either MOG35–55 or anti-CD3 induced proliferation as well as IL-2 production of effector T cells (CD4+CD25−) isolated from EAE mice spleen. Together, these findings suggest that Que displays an immune-modulating role during the course of EAE, and thus may be a promising candidate for treatment of MS.