The role of the brain-immune interaction in the environmental stress-induced immunomodulation

脑免疫相互作用在环境应激诱导的免疫调节中的作用

• 批准号: 04454144
• 负责人: HORI Tetsuo
• 金额: $ 4.1万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454144/
• 关键词: Interleukin-1beta; Prostaglandine; alpha-MSH; CRF; Splenic noradrenaline; Interferon palpha; Preoptic hypothalamus; Circumventricular organs; インターロイキン-1beta; alphaMSH; インターフェロンalpha; 免疫サイトカイン; 発熱高体温; インターロイキン-1; 脾臓交感神経; ナチュラルキラー細胞; 脳オピオイド

The aim of this project was to investigagte mechanisms of the environmental stress- induced immunosuppressionl Our findings are as follows. 1. The environmental stress and the hypothatmo-autonomic-immune system : (1) The cytotoxic activity of the splenic natural killer cells (NK activity) of rats was highest at the normal temperature (37-38ﾟC), while it was suppressed both at hyperthemia and hypothermia. This is obviously different from temperature sensitivity of T cells which are known to be most active at 39-40ﾟC.(2) Immobilization stress suppressed the splinic NK activity which was abolished by the surgical denervation of the spleen. An in vivo microdialysis of the spleen revealed that the release of the noradrenaline (NA) from the sympathetic nerve terminals markedly increased by the immobilizatin stress. (3) Central and peripheral injection of interleukin-1beta (IL-1 beta) increased the activity of the splenic nerve and the release of NA in the spleen, resulting in the suppression … More of the cellular immunity. The effects of IL-1 beta was found to be IL-1 receptor-mediated and alpha-MSH sensitive process, which was dependent on the prostaglandins (PGs) and the CRF system. 2. The mechanisms of the environmental stress-induced immunomodulation : We examined the effects of central interferon- alpha (IFN- plpha) on the splenic NK cell activity as an experimental model of opioid dependent stress-induced suppression of the cellular immunity. When recombinant human IFN- alpha, which is known to bind central opiod receptors in rats and mice, was microinjected into the preoptic/anterior hypothalamus (POA), the splenic sympathetic nerve activity increased through an activation the central CRF system. The enhancement of the nerve activity resulted in the suppression of the splenic NK activity through a beta -adrenetgic action. 3. Blood-borne immunocytokines and the hypothalamic neuronal activity : All neurons in the anteroventral region of the third ventricle (AV3V), which hThe results suggested that AV3V is important in the transduction mechanisms of blood-borne cytokines into brain signals. Less

本研究旨在探讨环境应激诱导免疫抑制的机制。1. (1)大鼠脾自然杀伤细胞的细胞毒活性（NK活性）在常温（37 ~ 38ºC）下最高，在高热和低温下均受到抑制。这与T细胞的温度敏感性明显不同，T细胞在39-40ºC时最活跃。(2)固定化应激可抑制spline NK活性，而这种活性被脾脏手术去神经支配所消除。脾体内微透析显示，在固定应激下，交感神经末梢的去甲肾上腺素（NA）的释放明显增加。(3)中央和外周注射白细胞介素-1 β (IL-1 β)可增加脾神经活性和脾内NA的释放，从而抑制细胞免疫。发现IL-1 β的作用是IL-1受体介导的α - msh敏感过程，该过程依赖于前列腺素（pg）和CRF系统。2. 环境应激诱导免疫调节的机制：我们研究了中枢干扰素- α (IFN- plpha)对脾脏NK细胞活性的影响，作为阿片依赖性应激诱导细胞免疫抑制的实验模型。重组人IFN- α可以结合大鼠和小鼠的中枢阿片受体，当将重组人IFN- α微注射到视前/下丘脑前部（POA）时，脾脏交感神经活动通过激活中枢CRF系统而增加。神经活性的增强通过肾上腺素作用抑制脾脏NK活性。3. 血源性免疫细胞因子与下丘脑神经元活性的关系：第三脑室前腹侧区（AV3V）的所有神经元均存在，结果提示AV3V在血源性细胞因子转化为脑信号的转导机制中起重要作用。少

项目成果

堀 哲郎: "「老化と脳」(大村裕,大浦彦吉編)分担執筆“脳と免疫系の相互対話"(144〜163頁)" 共立出版, 277 (1992)

Tetsuro Hori：“‘衰老与大脑’（由 Hiroshi Omura 和 Hikoyoshi Oura 编辑）合着‘大脑与免疫系统之间的相互作用’（第 144-163 页）”Kyoritsu Shuppan，277（1992）

Take,S.: "Central interferon alpha inhibits the natural killer cytotoxicity through sympathetic innervation." Am.J.Physiol.265. R453-R459 (1993)

Take,S.：“中枢干扰素α通过交感神经支配抑制自然杀伤细胞毒性。”

Aou,S.: "The stomach is the etiological organ for immobilization-induced hypocalcemia in the rat." Am.J.Physiol.265. R1376-R1379 (1993)

Aou,S.：“胃是大鼠固定引起的低钙血症的病因器官。”

堀哲郎.: "脳と免疫系." 生体の科学. 44. 548-549 (1993)

Tetsuro Hori.：“大脑和免疫系统。”44。548-549（1993）

堀 哲郎: "免疫系による神経系の調節・発熱.「神経内分泌免疫学」" 朝倉書店(井村裕夫、堀 哲郎、村松 繁編), 312(185-197) (1993)

堀哲郎：“免疫系统对神经系统和发热的调节。‘神经内分泌免疫学’”朝仓书店（井村广夫、堀哲郎、村松茂编辑），312(185-197) (1993)