Roles of brain cytokines and sympathetic nervous system in neural immune interaction during environmental stress.

环境应激期间脑细胞因子和交感神经系统在神经免疫相互作用中的作用。

• 批准号: 05454143
• 负责人: KATAFUCHI Toshihiko
• 金额: $ 4.29万
• 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: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454143/
• 关键词: Splenic sympathetic nerve; interleukin-1beta; interferon-alpha; corticotropin-releasing factor; prostaglandin E2; anterventral region of the III vetricle; glial cell; long term potentiation; EP1レセプター; c-fosタンパク; アンチセンスオリゴDNA; TNF; グルタミン酸; 第3脳

What we found by this project is as follows.(1) Suppression of splenic natural killer (NK) cell activity by noradrenaline released from splenic sympathetic nerve (SSN) terminals is one of the mechanisms of immobilization-induced immunosuppression. (2) Brain IL-1beta induces reduction of cellular immunity at least partly through an activation of the SSN.(3) Immunosuppression induced by both brain IFN-alpha and IL-1beta is due to an activation of CRF system which leads to an enhancement of the SSN.(4) EP1 receptors for PGE2 are partly involved in the activation of brain CRF system. (5) 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 SSN.(6) Splenic NK activity decreases during dynamic phase of the ventromedial hypothalamus (VMH) lesiong-induced hyperphagia, while it increases during static phase. (7) An expression of c-fos protein in the MPO is important in thermoregulation during an exposure to high temperature. (8) An expression of IFN-alpha mRNA enhances by the immoblization stress in mouse. (9) Neurons in the anteroventral region of the III ventricle projecting to the MPO and the paraventricular nucleus play an important role in blood-borne cytokine-brain signal transduction. (10) Inhibition of the dorsal vagal motoneurons by IL-1beta through the prostanoids is considered to be one of the mechanisms of the IL-1beta-induced suppression of gastric acid secretion. (11) TNF-alpha inhibits the VMH neuronal activity, while TNF-beta activates it. (12) IFN-alpha suppresses the NMDA-induced inward current through the second mediators such as superoxide and nitric oxide. (13) The suppression of the NMDA-induced responses by IFN-alpha occurs only in the presence of the glial cells. PGE2 enhances the Ca^<2+> dependent K^+ current induced by glutamate. (14) IL-6 suppresses the long term potentiation in the hippocampal CA1 region.

本课题的研究结果如下：(1)脾交感神经末梢释放的去甲肾上腺素抑制脾自然杀伤(NK)细胞活性是固定化诱导免疫抑制的机制之一。(2)脑IL-1β至少部分通过激活SSN导致细胞免疫功能下降。(3)脑内α-干扰素和IL-1β诱导的免疫抑制是由于CRF系统激活导致SSN增强。(4)PGE2的EP1受体部分参与了脑CRF系统的激活。(5)内侧视前区(MPO)是干扰素-α最有效的作用部位，通过对SSN的抑制作用参与免疫的中枢调节。(6)腹内侧部下丘脑(VMH)诱导的吞噬功能亢进时，脾NK活性动态降低，静止期升高。(7)在高温条件下，MPO中c-fos蛋白的表达在体温调节中起重要作用。(8)束缚应激可增强小鼠脑内α-干扰素的表达。(9)三脑室前腹侧区投射至MPO和室旁核的神经元在血源性细胞因子脑信号转导中起重要作用。(10)IL-1β通过前列腺素对迷走背侧运动神经元的抑制作用被认为是IL-1β抑制胃酸分泌的机制之一。(11)TNF-α抑制VMH神经元的活动，而TNF-β激活VMH神经元的活动。(12)干扰素-α可通过超氧化物和一氧化氮等第二介质抑制NMDA诱导的内向电流。(13)只有在胶质细胞存在的情况下，干扰素-α才能抑制NMDA诱导的反应。前列腺素E_2增强谷氨酸诱导的钙依赖钾电流。(14)IL-6抑制大鼠海马CA1区的长时程增强。

项目成果

Hori, T.: "The autonomic nervous system as a communication channel between the brain and the immmune system." Neuroimmunomodulation. (in press). (1996)

Hori, T.：“自主神经系统是大脑和免疫系统之间的沟通渠道。”

Katafuchi, T.et al.: "Hypothalamic modulation of splenic natural killer cell activity in rats." Journal of Physiology (Lond.). 471. 209-221 (1993)

Katafuchi, T.等人：“下丘脑对大鼠脾脏自然杀伤细胞活性的调节。”

Hori, T.et al.: "The hypothalamo-sympathetic nervous system modulates peripheral cellular immunity." Neurobiology. (in press). (1996)

Hori, T.et al.：“下丘脑交感神经系统调节外周细胞免疫。”

片渕俊彦: "脳と免疫のクロストーク:視床下部-交感神経系による免疫系の制御." ブレインサイエンス. 5(4). 381-387 (1994)

Toshihiko Katabuchi：“大脑和免疫之间的串扰：下丘脑交感神经系统对免疫系统的控制。” 5(4) (1994)。

堀哲郎: "脳・免疫系関連と発熱." 第24回日本医学会総会会誌. II. 538-539 (1995)

Tetsuro Hori：“脑免疫系统的关系和发烧”，日本医学会第 24 届大会杂志 II 538-539。