Methylprednisolone induces reversible clinical and pathological remission and loss of lymphocyte reactivity to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis
Methylprednisolone induces reversible clinical and pathological remission and loss of lymphocyte reactivity to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis
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DOI：
10.1080/08916930802011258
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发表时间：
2008-01-01
期刊：
影响因子：
3.5
通讯作者：
Alderuccio, Frank
中科院分区：
文献类型：
--
作者：
Chan, James;Ban, Ee Jun;Alderuccio, Frank
实验性自身免疫性脑脊髓炎（EAE）是人类多发性硬化症（MS）的动物模型。EAE由髓鞘相关自身抗原免疫诱导，其特征在于中枢神经系统（CNS）中的炎性浸润，与轴突变性、脱髓鞘和损伤相关。我们最近在实验性小鼠自身免疫性胃炎模型中发现，甲基强的松龙治疗可诱导胃炎的可逆缓解，并伴有胃粘膜的再生。在这里，我们研究了口服甲基强的松龙对由髓鞘少突胶质细胞糖蛋白肽（MOG（35-55））免疫诱导的人MS的小鼠EAE模型的影响。我们检查了治疗和停用类固醇后的临床评分、CNS病理学和淋巴细胞对MOG（35-55）的反应性。甲基强的松龙缓解了EAE的临床体征和CNS中的炎性浸润，伴随着对MOG（35-55）肽的淋巴细胞反应性的丧失。甲基强的松龙停药引起临床特征复发，CNS炎性浸润和淋巴细胞对MOG（35-55）肽的反应性恢复。这是第一项研究表明，甲基强的松龙诱导可逆缓解的临床和病理特征的EAE小鼠伴随着损失的淋巴细胞反应性的致脑炎原。该模型将有助于更好地了解与类固醇诱导的疾病缓解，复发和髓鞘再生相关的机制的研究，也是一个重要的辅助整体治疗策略。
Experimental autoimmune encephalomyelitis (EAE) is an animal model of human multiple sclerosis (MS). EAE, induced by immunisation with myelin-associated autoantigens, is characterised by an inflammatory infiltrate in the central nervous system (CNS) associated with axonal degeneration, demyelination and damage. We have recently shown in an experimental mouse model of autoimmune gastritis that methylprednisolone treatment induces a reversible remission of gastritis with regeneration of the gastric mucosa. Here, we examined the effect of oral methylprednisolone on the mouse EAE model of human MS induced by immunisation with myelin oligodendrocyte glycoprotein peptide (MOG(35-55)). We examined the clinical scores, CNS pathology and lymphocyte reactivity to MOG(35-55) following treatment and withdrawal of the steroid. Methylprednisolone remitted the clinical signs of EAE and the inflammatory infiltrate in the CNS, accompanied by loss of lymphocyte reactivity to MOG(35-55) peptide. Methylprednisolone withdrawal initiated relapse of the clinical features, a return of the CNS inflammatory infiltrate and lymphocyte reactivity to MOG(35-55) peptide. This is the first study to show that methylprednisolone induced a reversible remission in the clinical and pathological features of EAE in mice accompanied by loss of lymphocyte reactivity to the encephalitogen. This model will be useful for studies directed at a better understanding of mechanisms associated with steroid-induced disease remission, relapse and remyelination and also as an essential adjunct to an overall curative strategy.