MECHANISM OF ACTION OF CYTOKINES ON BRAIN AND PITUITARY

细胞因子对脑和垂体的作用机制

• 批准号: 2675183
• 负责人: SAMUEL M MCCANN
• 金额: $ 27.81万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2675183
• 关键词: AIDS dementia complex; FK506; arachidonate; brain; calcium; cyclosporines; cytokine; dexamethasone; hypothalamic pituitary axis; hypothalamus; interferon gamma; interleukin 1; interleukin 2; interleukin 6; laboratory rat; melanocyte stimulating hormone; nervous system infection; nitric oxide; physical chemical interaction; pituitary gland; thymosin; toxic shock syndrome; tumor necrosis factor alpha

We have characterized the actions on the hypothalamic-pituitary axis of a number of cytokines which include interleukin-1 (IL-1), IL-2, lL-6, tumor necrosis factor (TNFalpha), gamma-interferon and thymosin alpha1. The hypothesis is that the pattern of hypothalamic-pituitary hormone release that is brought about by infection is induced by these various cytokines which are released as a result of the stimulation of their production and release by bacterial and viral endotoxins. All of these cytokines appear to have actions, both on the hypothalamus and the anterior pituitary gland with the rapid effects mediated via hypothalamic action and the slower effects mediated by combined hypothalamic-pituitary actions. Because excessive release and actions of cytokines are very damaging in a number of diseases, agents which block their action may have great therapeutic value. Consequently, this research is aimed at identifying the site of action, the molecular mechanism of action and pathophysiologic significance of cytokines thought to play a role in the development of the CNS and hypothalamic-pituitary pathology in AIDS with the view that agents which can block the action of these cytokines might be of value in the treatment of patients with AIDS, and other conditions such as toxic shock associated with excess production and action of cytokines. It is the purpose of this grant to determine the cell type on which these various cytokines are acting both in the hypothalamus and in the pituitary to modify the release of hypothalamic and pituitary hormones and their molecular mechanism of action at both hypothalamic and pituitary sites. These anticytokine agents might also be valuable, particularly in acute conditions such as toxic shock associated with excess production and action of cytokines.

我们已经描述了下丘脑-垂体轴的作用 细胞因子的数量，包括白介素-1 (IL-1)、IL-2、IL-6、肿瘤 坏死因子 (TNFα)、γ-干扰素和胸腺素 α1。 这 假设是下丘脑-垂体激素释放的模式 感染引起的病毒是由这些不同的细胞因子诱导的 它们是由于刺激其生产而释放的 细菌和病毒内毒素释放。 所有这些细胞因子都出现 对下丘脑和垂体前叶都有作用 通过下丘脑作用介导的快速作用和较慢的作用 由下丘脑-垂体联合作用介导的作用。 因为 细胞因子的过度释放和作用在许多方面都具有很大的破坏性 对于多种疾病，阻断其作用的药物可能具有很好的治疗作用 价值。 因此，本研究的目的是确定 作用、作用分子机制和病理生理学 被认为在细胞发育中发挥作用的细胞因子的重要性 艾滋病中的中枢神经系统和下丘脑-垂体病理学认为，药物 可以阻断这些细胞因子的作用，可能在以下方面有价值： 治疗艾滋病患者以及中毒性休克等其他病症 与细胞因子的过量产生和作用有关。 它是 这笔拨款的目的是确定这些不同的细胞类型 细胞因子同时作用于下丘脑和垂体 改变下丘脑和垂体激素的释放及其 下丘脑和垂体部位作用的分子机制。 这些抗细胞因子药物也可能很有价值，特别是在急性 诸如与过量生产相关的中毒性休克等情况 细胞因子的作用。