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 回应。白介素1、白介素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，均 三种细胞因子增加脑色氨酸，IL-1和IL-6均增加 大脑5-羟色胺代谢。这三种细胞因子都与一种 行为变化多种多样，但IL-1显然是最活跃和最有效的。 由细胞因子引起的变化类似于与感染和 受伤使他们成为免疫系统信使的首选对象 大脑。这一提议旨在阐明通过什么机制 细胞因子改变中枢神经系统的功能。具体目标是 确定细胞因子对脑去甲肾上腺素能影响的意义 和5-羟色胺能系统，特别是它们与HPA激活的关系 和行为。去甲肾上腺素对IL-1的反应与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需的 用于IL-1激活HPA。前列腺素合成似乎参与了 HPA的激活，以及神经化学和行为反应，但可能不 是必要的。色氨酸和5-羟色胺变化的意义是 未知。具体的实验目标是：确定 去甲肾上腺素参与IL-1诱导的HPA活化确定角色的步骤 环氧合酶(COX)参与HPA、神经化学和行为的研究 对IL-1的反应。确定机制(S)通过哪个外周 给予IL-6可激活小鼠的HPA轴。并且，为了确定 脑内色氨酸和5-羟色胺代谢增加的机制 对IL-1β、IL-6和内毒素的反应。

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.