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

通过这个项目我们发现如下。(1)脾交感神经末梢释放的去甲肾上腺素抑制脾自然杀伤细胞（NK）活性是固定诱导免疫抑制的机制之一。(2)脑il -1 β至少部分通过激活SSN诱导细胞免疫降低。(3)脑ifn - α和il -1 - β诱导的免疫抑制是由于CRF系统的激活导致SSN的增强。(4) PGE2的EP1受体部分参与脑CRF系统的激活。(5)内侧视前区（medial preoptic area， MPO）是ifn - α最有效的作用部位，通过对SSN的抑制作用参与免疫中枢调控。(6)下丘脑腹内侧（VMH）损伤性贪食在动态期脾脏NK活性降低，在静态期脾脏NK活性升高。(7) MPO中c-fos蛋白的表达在高温下的体温调节中起重要作用。(8)小鼠固定化应激增强ifn - α mRNA的表达。(9)第三脑室前腹侧区神经元向MPO和室旁核投射，在血源性细胞因子-脑信号转导中起重要作用。（10） il -1 β通过前列腺素抑制迷走背运动神经元被认为是il -1 β诱导的胃酸分泌抑制的机制之一。（11） tnf - α抑制VMH神经元活性，而tnf - β激活VMH神经元活性。（12） ifn - α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） ifn - α对nmda诱导反应的抑制仅发生在胶质细胞存在的情况下。PGE2增强谷氨酸诱导的Ca^<2+>依赖性K^+电流。（14） IL-6抑制海马CA1区的长时程增强。

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.