Cytokine Action on the CNS

描述：神经系统和免疫系统之间的适当相互作用 对宿主防御很重要感染、伤害和其他挑战， 免疫系统诱导细胞因子的产生。细胞因子给药 可引起电生理、内分泌、神经化学和行为 应答白细胞介素-1（IL-1）、白细胞介素-6（IL-6）与肿瘤坏死 因子-α（TNF-α）激活下丘脑-垂体-肾上腺（HPA）轴。 IL-1和TNF-α增加大脑去甲肾上腺素能神经元的活性，所有 三种细胞因子增加脑色氨酸，IL-1和IL-6都增加， 脑血清素代谢所有这三种细胞因子都参与了一种 各种行为变化，但IL-1显然是最活跃和最有效的。 由细胞因子诱导的变化类似于与感染相关的变化， 使它们成为免疫系统信使的主要候选者， 大脑这一提议旨在阐明 细胞因子改变中枢神经系统功能。具体目标是 确定细胞因子对脑去甲肾上腺素能神经元的影响的意义， 和肾上腺素能系统，特别是它们与HPA激活的关系 和行为。IL-1的去甲肾上腺素能反应与HPA密切相关 激活，但一些证据表明，去甲肾上腺素可能不是必要的， IL-1激活HPA。前列腺素的合成似乎与 HPA激活，以及神经化学和行为反应，但可能不会 是必要的。色氨酸和5-羟色胺变化的意义在于 未知具体的实验目标是： NE参与IL-1引起的HPA活化。为了确定角色 环氧合酶（考克斯）参与HPA、神经化学和行为学 对IL-1的反应要确定外围设备 IL-6的施用激活小鼠中的HPA轴。为了确定 脑色氨酸和5-羟色胺代谢增加的机制 对IL-1 β、IL-6和LPS的应答。

DESCRIPTION: Appropriate interactions between the nervous and immune systems are important for host defense. Infections, injuries and other challenges to the immune system induce the production of cytokines. Cytokine administration can elicit electrophysiological, endocrine, neurochemical and behavioral responses. Interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) activate the hypothalamo-pituitary-adrenal (HPA) axis. IL-1 and TNF-alpha increase the activity of cerebral noradrenergic neurons, all three cytokines increase brain tryptophan, and both IL-1 and IL-6 increase brain serotonin metabolism. All three cytokines have been implicated in a variety of behavioral changes, but IL-1 is clearly the most active and potent. The changes induced by cytokines resemble those associated with infection and injury making them prime candidates for messengers from the immune system to the brain. This proposal is designed to elucidate the mechanisms by which cytokines alter central nervous system function. The specific goal is to determine the significance of the effects of cytokines on brain noradrenergic and serotonergic systems, in particular their relationship to HPA activation and behavior. The noradrenergic responses to IL-1 is closely related to the HPA activation, but some evidence suggests that norepinephrine may not be necessary for HPA activation by IL-1. Prostaglandin synthesis appears to be involved in the HPA activation, and the neurochemical and behavioral responses, but may not be necessary. The significance of the changes in tryptophan and serotonin is unknown. Specific experimental objectives are: To determine the nature of the involvement of NE in the HPA activation caused by IL-1. To determine the role of cyclooxygenase (COX) involvement in the HPA, neurochemical, and behavioral responses to IL-1. To determine the mechanism(s) by which peripheral administration of IL-6 activates the HPA axis in mice. And, to determine the mechanisms of the increases in brain tryptophan and serotonin metabolism in response to IL-1beta, IL-6 and LPS.