Roles of Cytokines in Stress-induced Immune Responses

细胞因子在应激诱导的免疫反应中的作用

基本信息

批准号：
08044300
负责人：
HORI Tetsuro
金额：
$ 1.92万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

In this project, we are going to clarify the mechanisms how the neuroimmuno-endocrine network funcations as the host-defense system against the environmental stress. What we found in this project is as follows ; 1) Interleukin-6 inhibits long-term potentiotion in rat hippocampal neurons. 2) Tumor necrosis factor alpha not beta suppressed neuronal activity in the ventromedial hypothalamic neurons in vitro. 3) The mRNA of interferon alpha in the brain increased during immobilization stress. The medial preoptic area (MPO), which is the most potent acting site of IFN alpha, is involved in the central regulation of immunity by its suppressive influence on the splenic sympathetic nervous activity. 4) The c-fos protein expressed in the POA during hyper and hypothermic condition. Microinjection of antisense oligonucreotide for c-fos into the POA decreased body temperature. 5) Both IL-1 beta mRNA tissue content in the hypothalamus, the pituitary, and the liver but not in the hippocampus and the spleen increased by immobilization stress for 30 min. 6) Delayd cell death in the CAI neurons induced by brain ischemia was protected by continuous infusion of PACAP either intothe brain or in to the jugular vein. Since IL-6 concentration in the CSF increased by continuous infusion of PACAP,the tropic effect of PACAP on neurons might be, at least partly, mediated by brain cytokines. 7) The IM-induced IL-6 increase is completely abolished by in vivo neutralization of LPS.8) The concentration of LPS in the hepatoportal vein increases during IM.9) A fluorescent dye (FITC)-labeled LPS injected into the intestinal lumen is detected in Kupffer cells and sinusoidal endothelial cells after IM,78% of which are also stained with an anti-IL-6 antibody. The results suggest the presence of a brain-gut-liver immune axis, which is activated during pschophysical stresses.

在这个项目中，我们将阐明神经免疫内分泌网络如何作为宿主防御系统对抗环境压力的机制。我们在这个项目中发现的内容如下； 1) Interleukin-6 抑制大鼠海马神经元的长时程增强。 2) 体外肿瘤坏死因子α而不是β抑制下丘脑腹内侧神经元的神经元活动。 3) 大脑中干扰素α的mRNA在固定应激期间增加。内侧视前区（MPO）是 IFN α 最有效的作用位点，通过抑制脾交感神经活动参与免疫的中枢调节。 4）在高温和低温条件下POA中表达的c-fos蛋白。将 c-fos 反义寡核苷酸显微注射到 POA 中可降低体温。 5)固定应激30分钟后，下丘脑、垂体和肝脏中的IL-1β mRNA组织含量均增加，但海马和脾中不增加。 6)通过将PACAP持续输注到大脑或颈静脉中，可以保护由脑缺血引起的CAI神经元中的延迟细胞死亡。由于连续输注 PACAP 会增加 CSF 中的 IL-6 浓度，因此 PACAP 对神经元的趋向作用可能至少部分是由脑细胞因子介导的。 7) IM 诱导的 IL-6 增加被 LPS 的体内中和完全消除。8) IM 期间肝门静脉中的 LPS 浓度增加。9) 将荧光染料 (FITC) 标记的 LPS 注射到肠腔中IM 后在库普弗细胞和窦内皮细胞中检测到，其中 78% 也被抗 IL-6 抗体染色。结果表明存在脑-肠-肝免疫轴，该轴在心理压力期间被激活。