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

我们通过这个项目发现如下。(1)脾交感神经（SSN）末梢释放的去甲肾上腺素抑制脾自然杀伤（NK）细胞活性是制动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诱导细胞免疫力降低。(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)PGE_2的EP_1受体部分参与脑CRF系统的激活。(5)视前内侧区（MPO）是IFN-α最有效的作用部位，通过其对SSN的抑制作用参与免疫的中枢调节。(6)脾NK活性在下丘脑腹内侧核（VMH）损伤诱导的高摄食的动态阶段降低，而在静态阶段增加。(7)MPO中c-fos蛋白的表达在高温暴露期间的体温调节中是重要的。(8)在小鼠中，IFN-α mRNA的表达通过固定应激而增强。(9)投射到MPO和室旁核的III脑室前腹侧区神经元在血传脑-脑信号转导中起重要作用。(10)IL-1 β通过前列腺素类抑制背迷走神经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神经元的活动，而TNF-β激活它。（12）IFN-α通过第二介质如超氧化物和一氧化氮抑制NMDA诱导的内向电流。(13)IFN-α对NMDA诱导的反应的抑制仅在神经胶质细胞存在的情况下发生。PGE 2增强谷氨酸诱导的Ca^2+依赖性K^+电流。(14)IL-6抑制海马CA 1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.