NEUROPEPTIDERGIC MEDIATION OF THE ACUTE PHASE REACTION

急性期反应的神经肽能介导

• 批准号: 3477340
• 负责人: WILLIAM D RUWE
• 金额: $ 8.36万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3477340
• 关键词: acute phase protein; antipyretic; arginine vasopressin; body temperature regulation; brain septal area; central nervous system; hyperthermia; interleukin 1; laboratory rabbit; laboratory rat; neural information processing; neuropeptides; phagocytes; preoptic areas; pyrogens

The response of an organism to infection, known as the acute phase reaction (APR), appears to be mediated primarily by soluble products of mononuclear phagocytes. These soluble mediators or endogenous pyrogens (EPs), such as interleukin-1 (IL-1), may act within the central nervous system (CNS) to mediate many of the changes associated with the APR. The anterior, preoptic area of the hypothalamus (AH/POA) represents one area of the CNS that is known to be sensitive to the EPs and believed to be part of the circuitry involved in the development of the thermal component of the APR. A series of experiments are proposed to elucidate the means by which central mechanisms influence fever and the APR. First, other sites in the CNS (e.g., the ventral septal area or VSA and the organum vasculosum lamina terminalis or OVLT), will be evaluated for their reactivity to the EPs and their involvement in the evocation of the APR. Second, the efficacy of perfusing antipyretics, both exogenous and endogenous (e.g., arginine vasopressin or AVP), directly into these sites in suppressing the thermal and nonthermal components of the APR will be examined. Third, the AVP-induced antagonism of the APR will be characterized using both in vitro and in vivo techniques. Fourth, the effects of electrical stimulation of cell bodies containing AVP on the pathogenesis of fever and the APR will be examined. Fifth, the role of the amines in the evocation and/or suppression of the APR will be determined. Utilizing a microperfusion technique, it will be possible to determine the role of EPs, brain peptides and other putative mediators in the pathogenesis of fever and the APR. The long term goals are to elucidate the mechanism by which pyrogens act to elicit the thermal and nonthermal components of the APR and to identify the means by which the CNS elaborates endogenous antipyretics to prevent the deleterious effects of hyperpyrexias. This information should prove useful in determining the manner in which the CNS directly influences immune, physiologic and hematologic functions during infection. As a result, it may be possible to develop specific therapeutic agents to reduce life-threatening pyrexic responses without precluding the potentially beneficial aspects of fever.

机体对感染的反应，称为急性 相反应(APR)，似乎主要是由可溶性 单核巨噬细胞的产物。这些可溶的调解物或 内源性热原(EP)，如白介素1(IL-1)可能起作用 在中枢神经系统(CNS)内调节许多 与APR关联的更改。前视前区 下丘脑(AH/POA)代表中枢神经系统的一个区域 已知对EP敏感，并被认为是 开发热部件所涉及的电路 在APR的。 提出了一系列实验来阐明这一方法 哪些中枢机制会影响发烧和APR。第一, 中枢神经的其他部位(如腹中隔区或VSA和 终板血管器或OVLT)， 评估他们对EP的反应性和他们参与的 《行政程序法》的召回。第二，灌流的功效 外源性和内源性(如精氨酸)退烧药 加压素或AVP)，直接进入这些部位，抑制 将检查APR的热组件和非热组件。 第三，AVP对APR的拮抗作用 同时使用体外和体内技术进行表征。第四, 电刺激含AVP的细胞体的作用 将对发热的发病机制和APR进行检查。 第五，胺在唤起和/或抑制中的作用 年利率的比例将会确定。利用微灌注法 技术，将有可能确定EPs，大脑的作用 多肽和其他可能的介质在发热发病中的作用 和APR。 长期目标是阐明通过什么机制 热源作用于诱导热成分和非热成分 APR并确定CNS详细说明的手段 内源性解热药预防胃肠病的不良反应 体温过高。这些信息将被证明对 确定中枢神经系统直接影响的方式 感染期间的免疫、生理和血液学功能。 因此，有可能开发出特定的治疗方法。 减少危及生命的发热反应的药物，而不是 排除了发烧可能有益的方面。