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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.

几种趋化因子及其相关受体的免疫反应性已在中枢神经系统的常驻细胞中得到证实，其中一些趋化因子的上调与单纯疱疹病毒性脑炎（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（8 OHdG）参与HES发病的可能性。我们研究了6例HSE患者、9例非疱疹性边缘脑炎（NHLE）患者、5例无菌性脑膜炎（AM）患者、5例急性弥漫性脑脊髓炎（ADEM）患者和13例非炎症性神经系统疾病患者。ELISA法检测脑脊液中趋化因子的浓度。在HSE、NHLE、AM和ADEM的CSF样本中，除GM-CSF和8-OHdG外，还可检测到6种趋化因子水平。与HSE、NHLE和AM相比，NHLE中IL-8浓度有升高趋势，AM中RANTES、MIP-1a浓度有升高趋势。然而，在这些组之间未观察到统计学差异。IP-10浓度在ADEM中显著升高，而MCP-1水平在ADEM中显著降低。这些IP-10增加和MCP-1减少的发现被认为是脱髓鞘神经系统疾病的特征。本研究测定了脑脊液中抗谷氨酸受体抗体（G1 uR Ab）。GluR Ab阳性5例（NHLE 3例，HSE 1例，ADEM 1例），阴性4例（NHLE 3例，HSE 1例）。与上述各组相比，GluR Ab阳性组各趋化因子水平均有升高趋势。CSF中存在多种特异性趋化因子，以响应炎症反应或自身免疫抗体的产生。