Intrathecal regulation of chemokine, oxidative stress, and inflammatory molecules on the pathogenesis of herpes simplex encephalitis

趋化因子、氧化应激和炎症分子的鞘内调节对单纯疱疹脑炎发病机制的影响

基本信息

批准号：
18590959
负责人：
NAKAJIMA Hideto
金额：
$ 1.75万
依托单位：
Osaka Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Immunoreactivity for several chemokines and for their related receptors has been demonstrated in resident cells of the central nervous system, and the up-regulation of some of them is associated with pathological changes found in herpes simplex encephalitis (HSE). We investigated the possibility of the involvement of IP-10, MCP-1, IL-8, RANTES, MIP-1a, sTNF-R1, GM-CSF, and 8-hydroxy-2'-deoxyguanosine (8OHdG) in HES pathogenesis. We studied 6 patients with HSE, 9 with non-herpetic limbic encephalitis (NHLE), 5 with aseptic meningitis (AM), 5 with acute disseminated encephalomyelitis (ADEM), and 13 with non-inflammatory neurological disease. The chemokine concentration were measured by ELISA in cerebrospinal fluid (CSF). Six chemokines levels except for GM-CSF and 8-OHdG were detectable in CSF samples from HSE, NHLE, AM, and ADEM. Comparison with HSE, NHLE, and AM, IL-8 concentration tended to increase in NHLE, and RANTES, MIP-1a concentration tended to increase in AM. However, statistical difference was not seen between these groups. IP-10 concentration was significantly increased in ADEM, whereas MCP-1 level was decreased in ADEM. These findings of increased IP-10 and decreased MCP-1 were thought to be features of demyelinated neurological disease. In the present study, anti-glutamate receptorantibodies (G1uR Ab) in CSF were measured. GluR Ab were positive in 5 cases (3 with NHLE, 1 with HSE, 1 with ADEM), and were negative in 4 cases (3 with NHLE, 1 with HSE). Compared with these groups, all chemokine levels tended to elevated in the GluR Ab positive group. Various and specific chemokines were present in the CSF in response to inflammatory reaction or production of auto-immune antibodies.

在中枢神经系统的驻留细胞中已经证明了几种趋化因子及其相关受体的免疫反应性，其中一些受体的上调与疱疹单纯脑炎（HSE）中发现的病理变化有关。我们研究了IP-10，MCP-1，IL-8，Rantes，MIP-1A，STNF-R1，GM-CSF和8-羟基-2'-脱氧鸟苷（8OHDG）参与的可能性。我们研究了6例HSE患者，9例非疱疹性边缘性脑炎（NHLE），5例患有无菌脑膜炎（AM），5例患有急性散布的脑脊髓炎（ADEM）和13例非炎性神经性神经疾病。通过ELISA在脑脊液（CSF）中通过ELISA测量趋化因子浓度。在HSE，NHLE，AM和ADEM的CSF样品中，可以检测到GM-CSF和8-OHDG以外的六个趋化因子水平。与HSE，NHLE和AM的比较，IL-8浓度在NHLE中倾向于增加，而MIP-1A浓度倾向于增加AM。但是，这些组之间没有看到统计差异。 ADEM的IP-10浓度显着增加，而ADEM的MCP-1水平降低。这些发现IP-10增加和MCP-1降低的发现被认为是脱髓鞘神经系统疾病的特征。在本研究中，测量了CSF中的抗谷氨酸受体抗体（G1UR AB）。 Glur AB在5例中为阳性（3例NHLE，1个带有HSE，ADEM 1），在4例中为阴性（3例NHLE，1例HSE）。与这些组相比，所有趋化因子水平在Glur AB阳性组中均趋于升高。 CSF中存在各种和特定的趋化因子，以应对炎症反应或自身免疫抗体的产生。