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Fingolimod Increases Brain-Derived Neurotrophic Factor Level Secretion from Circulating T Cells of Patients with Multiple Sclerosis.
CNS Drugs ( IF 6 ) Pub Date : 2019-12-01 , DOI: 10.1007/s40263-019-00675-7
Maya Golan 1 , Karin Mausner-Fainberg 1 , Bassima Ibrahim 2 , Moshe Benhamou 1, 3 , Adi Wilf-Yarkoni 4 , Hadar Kolb 4 , Keren Regev 4 , Arnon Karni 1, 2, 3, 4
Affiliation  

BACKGROUND The pathophysiology of multiple sclerosis involves an autoimmune and a neurodegenerative mechanism. Central nervous system-infiltrating immune cells in multiple sclerosis also possess a neuroprotective activity through secretion of neurotrophins, such as brain-derived neurotrophic factor. Fingolimod was shown to slow the progression of disability and loss of brain volume. OBJECTIVE The objective of this study was to explore whether fingolimod induces secretion of neurotrophins by immune cells. METHODS Blood was drawn from 21 patients before the initiation of treatment with fingolimod and at 6 and 12 months of follow-up. The levels of the neurotrophic factors brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, β-nerve growth factor, neurotrophin-3, neurotrophin-4, basic fibroblast growth factor, epidermal growth factor, and vascular endothelial growth factor were screened in the supernatants of separated T cells and monocyte cultures using a customized, multiplex enzyme-linked immunosorbent assay. Brain-derived neurotrophic factor levels were further validated by a specific enzyme-linked immunosorbent assay. RESULTS Treatment with fingolimod significantly increased brain-derived neurotrophic factor secretion from T cells. A specific enzyme-linked immunosorbent assay confirmed these results in the supernatant of T cells after 6 and 12 months of therapy. CONCLUSIONS T cells that reach the bloodstream of fingolimod-treated patients with multiple sclerosis may contribute to the neuroprotective effect of this therapy by increased secretion of brain-derived neurotrophic factor. This mechanism of action of fingolimod in patients with multiple sclerosis has not been previously reported.

中文翻译:

芬戈莫德提高多发性硬化症患者循环T细胞的脑源性神经营养因子水平分泌。

背景技术多发性硬化症的病理生理学涉及自身免疫和神经退行性机制。多发性硬化症中渗透到中枢神经系统的免疫细胞还通过分泌神经营养蛋白(例如脑源性神经营养因子)而具有神经保护活性。芬戈莫德被证明可以减缓残疾和脑容量的丧失。目的本研究的目的是探讨芬戈莫德是否能诱导免疫细胞分泌神经营养蛋白。方法在芬戈莫德治疗开始前以及随访6个月和12个月时,从21例患者中采血。神经营养因子的水平脑源性神经营养因子,神经胶质细胞源性神经营养因子,β神经生长因子,neurotrophin-3,neurotrophin-4,碱性成纤维细胞生长因子,使用定制的多重酶联免疫吸附试验,在分离的T细胞和单核细胞培养物的上清液中筛选了表皮生长因子和血管内皮生长因子。通过特定的酶联免疫吸附测定进一步验证了脑源性神经营养因子水平。结果芬戈莫德治疗可显着增加T细胞分泌脑源性神经营养因子。经过6和12个月的治疗,特异性酶联免疫吸附试验在T细胞上清液中证实了这些结果。结论到达芬戈莫德治疗的多发性硬化患者血液中的T细胞可能通过增加脑源性神经营养因子的分泌来促进这种疗法的神经保护作用。
更新日期:2019-11-01
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