Lithium prevents and ameliorates experimental autoimmune encephalomyelitis.
Lithium prevents and ameliorates experimental autoimmune encephalomyelitis.
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DOI：
10.4049/jimmunol.181.1.338
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发表时间：
2008-07-01
期刊：
影响因子：
--
通讯作者：
Jope RS
中科院分区：
文献类型：
--
作者：
De Sarno P;Axtell RC;Raman C;Roth KA;Alessi DR;Jope RS
实验性自身免疫性脑脊髓炎(EAE)模型，在动物身上具有多发性硬化症的许多特点，对此尚无适当的治疗方法。我们研究了糖原合成酶激酶-3(GSK3)的抑制剂锂是否可以改善小鼠的EAE。锂离子预处理可明显抑制髓鞘少突胶质细胞糖蛋白多肽(MOG35-55)免疫诱导的EAE小鼠的临床症状，并显著减少脱髓鞘、小胶质细胞活化和白细胞在脊髓中的浸润。发病后给予免疫后锂可降低病情严重程度，促进部分恢复。相反，在表达固有活性GSK3的敲入鼠中，EAE发展得更快、更严重。体内锂治疗抑制MOG35-55反应性效应T细胞分化，显著降低MOG35-55刺激的引流淋巴结和脾单个核细胞的增殖，以及MOG35-55诱导免疫小鼠脾细胞产生干扰素-γ、IL-6和IL-17。在蛋白脂蛋白多肽139-151诱导的复发/缓解性EAE中，在第一次临床发作后给予锂维持长期(免疫后90天)保护，停锂后病情迅速复发。这些结果表明，锂抑制EAE，并确认GSK3是一个新的抑制靶点，可能有助于多发性硬化症和其他困扰中枢神经系统的自身免疫性和炎症性疾病的治疗干预。
Experimental autoimmune encephalomyelitis (EAE) models, in animals, many characteristics of multiple sclerosis, for which there is no adequate therapy. We investigated whether lithium, an inhibitor of glycogen synthase kinase-3 (GSK3), can ameliorate EAE in mice. Pretreatment with lithium markedly suppressed the clinical symptoms of EAE induced in mice by myelin oligodendrocyte glycoprotein peptide (MOG35–55) immunization and greatly reduced demyelination, microglia activation, and leukocyte infiltration in the spinal cord. Lithium administered postimmunization, after disease onset, reduced disease severity and facilitated partial recovery. Conversely, in knock-in mice expressing constitutively active GSK3, EAE developed more rapidly and was more severe. In vivo lithium therapy suppressed MOG35–55-reactive effector T cell differentiation, greatly reducing in vitro MOG35–55-stimulated proliferation of mononuclear cells from draining lymph nodes and spleens, and MOG35–55-induced IFN-γ, IL-6, and IL-17 production by splenocytes isolated from MOG35–55-immunized mice. In relapsing/remitting EAE induced with proteolipid protein peptide139–151, lithium administered after the first clinical episode maintained long-term (90 days after immunization) protection, and after lithium withdrawal the disease rapidly relapsed. These results demonstrate that lithium suppresses EAE and identify GSK3 as a new target for inhibition that may be useful for therapeutic intervention of multiple sclerosis and other autoimmune and inflammatory diseases afflicting the CNS.
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DOI：
10.1016/0162-3109(91)90045-z
发表时间：
1991-11-01
期刊：
IMMUNOPHARMACOLOGY
影响因子：
--
作者：
LEVINE, S;SALTZMAN, A
通讯作者：
SALTZMAN, A
影响因子：
4.4
作者：
Axtell, Robert C.;Xu, Liang;Raman, Chander
通讯作者：
Raman, Chander
影响因子：
8.8
作者：
Dugo, Laura;Collin, Marika;Thiemermann, Christoph
通讯作者：
Thiemermann, Christoph
影响因子：
82.9
作者：
Heppner, FL;Greter, M;Aguzzi, A
通讯作者：
Aguzzi, A
DOI：
10.1016/0192-0561(94)90056-6
发表时间：
1994-10-01
期刊：
INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY
影响因子：
--
作者：
HART, DA;DONE, SJ;LENZ, SP
通讯作者：
LENZ, SP