Fingolimod alters inflammatory mediators and vascular permeability in intracerebral hemorrhage
Fingolimod alters inflammatory mediators and vascular permeability in intracerebral hemorrhage
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芬戈莫德改变脑出血中的炎症介质和血管通透性
DOI：
10.1007/s12264-015-1532-2
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发表时间：
2015-12-01
影响因子：
5.6
通讯作者：
Yan, Yaping
中科院分区：
文献类型：
--
作者：
Li, Yu-Jing;Chang, Guo-Qiang;Yan, Yaping
脑出血（ICH）导致高死亡率和残疾率。ICH后迅速出现的明显炎症反应有助于疾病进展。我们最近的临床试验表明，口服免疫调节剂芬戈莫德抑制继发性损伤源于初始血肿，但机制仍不清楚。在本研究中，我们的目的是研究芬戈莫德对炎症介质和血管通透性的影响，在临床试验中口服芬戈莫德治疗脑出血（ICH）。结果表明，芬戈莫德可降低外周血CD 4 +T、CD 8 +T、CD 19 +B、NK、NKT细胞数量，停药后迅速恢复。芬戈莫德可降低血浆ICAM水平，升高IL-10水平。有趣的是，芬戈莫德保护血管通透性，如MMP 9的血浆水平降低和rT1%降低所示。总之，芬戈莫德对全身炎症的调节表明其是ICH的有效治疗剂。芬戈莫德可能通过保护血管通透性来防止血肿周围水肿扩大。
Intracerebral hemorrhage (ICH) leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated that oral administration of an immune modulator fingolimod restrained secondary injury derived from initial hematoma, but the mechanisms remain unknown. In this study, we aim to investigate the effects of fingolimod on inflammatory mediators and vascular permeability in the clinical trial of oral fingolimod for intracerebral hemorrhage (ICH). The results showed that fingolimod decreased the numbers of circulating CD4+T, CD8+T, CD19+B, NK, and NKT cells and they recovered quickly after the drug was stopped. The plasma ICAM level was decreased and IL-10 was increased by fingolimod. Interestingly, fingolimod protected vascular permeability as indicated by a decreased plasma level of MMP9 and the reduced rT1%. In conclusion, modulation of systemic inflammation by fingolimod demonstrates that it is an effective therapeutic agent for ICH. Fingolimod may prevent perihematomal edema enlargement by protecting vascular permeability.