ALCOHOL AND BRAIN INTERLEUKIN 1

酒精和脑白细胞介素 1

• 批准号: 2000972
• 负责人: LEONARD P KAPCALA
• 金额: $ 10.46万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2000972
• 关键词: RNase protection assay; alcoholism /alcohol abuse; artificial immunosuppression; astrocytes; embryo /fetus tissue /cell culture; embryo /fetus toxicology; ethanol; gene induction /repression; hypothalamic pituitary axis; hypothalamus; immunocytochemistry; interleukin 1; laboratory rat; microglia; neuroimmunomodulation; neurons; nutrition related tag

APPLICANT S ABSTRACT: Alcohol (ethanol-ETOH) abuse produces pathological effects including various brain dysfunction and immune impairment associated with increased susceptibility to various infections. One central abnormality is EtOH activation of the hypothalamic-pituitary-adrenal (HPA) axis. Although stimulation of hypothalamic corticotropin-releasing hormone (CRH) producing neurons is critical for EtOH-induced HPA activation, a precise understanding of how this occurs remains to be established. Of potential relevance, interleukin (IL)-l potently stimulates the HPA axis, is produced in hypothalamus, and stimulates common cellular signals as EtOH. Preliminary results in our laboratory show that EtOH increases IL-1beta mRNA in primary hypothalamic neuronal and glial cultures. Thus, EtOH could activate the HPA axis by increasing hypothalamic IL-1 signaling. The proposed hypothesis is that EtOH induces hypothalamic IL-1, in vitro and in vivo studies will demonstrate: 1) effects of acute and chronic EtOH on expression of IL-1beta mRNA(RNase protection assay) and IL-1beta (immunocytochemistry-ICC) and on immune/cytokine stimulation in fetal rat hypothalamic neuronal, astrocytic and microglial cultures, and 2) effects of an EtOH diet on adult rat hypothalamic IL-1beta mRNA and IL-1beta and HPA axis activation. HPA axis activation occurs in alcoholics and can cause peripheral immunosuppression via glucocorticoid-dependent and -independent mechanisms. Recognizing that central effects of IL-1 can also cause peripheral immunosuppression via both these pathways, EtOH induction of brain IL-1 could lead to immunosuppression via these central mechanisms. The well recognized impaired immunity in alcoholics could be further attenuated by mechanisms involving central cytokine dysfunction which could contribute to the high prevalence of HIV infection in alcoholics and progression to AIDS. Long term goals are to learn about mechanisms mediating EtOH effects on the brain IL-1 system and to determine the role and significance of these alterations relative to EtOH-induced HPA axis activation and peripheral immunosuppression.

申请人摘要：酒精（乙醇-ETOH）滥用会产生病理性 影响包括各种脑功能障碍和免疫损伤相关 对各种感染的易感性增加。 一个中央 异常是下丘脑-垂体-肾上腺（HPA）的EtOH激活 轴线 虽然刺激下丘脑促肾上腺皮质激素释放激素 (CRH)产生神经元是EtOH诱导的HPA激活的关键， 对这种情况如何发生的确切理解仍有待确定。 的 潜在的相关性，白细胞介素（IL）-l有力地刺激HPA轴，是 产生于下丘脑，并刺激常见的细胞信号，如EtOH。 我们实验室的初步结果表明，乙醇增加IL-1 β mRNA 在原代下丘脑神经元和神经胶质培养物中。 因此，EtOH可以 通过增加下丘脑IL-1信号传导激活HPA轴。 的 提出的假设是，乙醇诱导下丘脑IL-1，在体外和体内， 体内研究将证明：1）急性和慢性EtOH对 IL-1 β mRNA表达（RNA酶保护试验）和IL-1 β （免疫细胞化学-ICC）和对胎鼠免疫/细胞因子刺激的影响 下丘脑神经元、星形胶质细胞和小胶质细胞培养物，和2） EtOH饮食对成年大鼠下丘脑IL-1 β mRNA和IL-1 β及HPA的影响 轴激活。 HPA轴激活发生在酗酒者中， 通过糖皮质激素依赖性和非依赖性机制的免疫抑制。 认识到IL-1的中枢作用也可引起外周 通过这两种途径的免疫抑制，EtOH诱导脑IL-1 可能通过这些中枢机制导致免疫抑制 井 酗酒者公认的免疫力受损可以进一步减弱， 涉及中枢细胞因子功能障碍的机制， 酗酒者中艾滋病毒感染率高，并发展为艾滋病。 长期目标是了解介导EtOH影响的机制， 脑IL-1系统，并确定这些作用和意义 相对于EtOH诱导的HPA轴激活和外周 免疫抑制