NEUROPEPTIDERGIC MEDIATION OF THE ACUTE PHASE REACTION

急性期反应的神经肽能介导

• 批准号: 3477338
• 负责人: WILLIAM D RUWE
• 金额: $ 7.12万
• 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/3477338
• 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.

生物体对感染的反应，称为急性 相反应（APR），似乎主要是由可溶性 单核吞噬细胞的产物。 这些可溶性介质或 内源性致热原（EP），如白细胞介素-1（IL-1），可能起作用， 在中枢神经系统（CNS）中介导许多 与APR相关的变化。 下丘脑（AH/POA）代表CNS的一个区域， 已知对EP敏感，并被认为是 涉及热元件开发的电路 的APR。 提出了一系列的实验来阐明的手段， 哪些中枢机制影响发热和APR。首先， CNS中的其它位点（例如，腹侧隔区或VSA， 终板血管器（OvLT），将是 评估他们对EP的反应性以及他们参与 第二，灌注的功效， 退热剂，包括外源性和内源性（例如，精氨酸 加压素或AVP），直接进入这些位点，抑制 将检查APR的热和非热组件。 第三，AVP诱导的APR拮抗作用将是 使用体外和体内技术表征。 第四、 电刺激含AVP的细胞体的作用 对发热和APR的发病机制进行研究。 第五，胺在唤起和/或抑制中的作用。 将被确定。 利用微灌注 技术，将有可能确定EP的作用，大脑 发热发病机制中的肽和其他假定介质 和APR。 长期目标是阐明 致热原的作用是引出热和非热成分， APR，并确定CNS阐述的方法 内源性解热药，以防止 高热 这些信息应该证明是有用的， 确定中枢神经系统直接影响 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， 排除了发烧的潜在益处。