CENTRAL MONOAMINES AND OPIOIDS IN ACUTE-PHASE REACTION

急性期反应中的中心单胺和阿片类药物

• 批准号: 3405544
• 负责人: CLARK M BLATTEIS
• 金额: $ 10.07万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1990-09-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3405544
• 关键词: brain mapping; brain metabolism; hyperthermia; interleukin 1; laboratory rabbit; neural information processing; neuropeptides; neurotransmitter metabolism; preoptic areas

Infected adults characteristically exhibit, in addition to fever, a concatenation of nonspecific host responses, termed the acute-phase reaction (APR). These include: neutrophilic leukocytosis, changes in the concentrations of certain plasma proteins and trace metals, and various other associated adjustments. It has long been known that the fever of infection is mediated by an endogenous factor from macrophages/monocytes, called Interleukin I (IL1). During the past decade, evidence has accumulated indicating that the nonthermal components of the APR also are mediated by IL1. It is well established that the primary site of the febrile action of IL1 is the preoptic are (PO) of the hypothalamus. Subsidiary IL1-sensitive sites that can drive fever have been localized in the lateral hypothalamus, pons, and medulla. Recent results from my laboratory indicate that the PO also is involved importantly in the regulation of certain nonthermal acute-phase responses to IL1, in particular the hepatic synthesis of glycoproteins. The data further suggest that the preoptic units that activate the febrile and nonfebrile responses to IL1 may be distinct. These proposed studies, therefore, are directed toward analyzing further the neural systems in the PO mediating the acute-phase reaction. Specifically, they are designed to determine whether the monoamines and the opioids, two classes of neurochemical substances with possible roles in fever production, might also be implicated in the control of the nonthermal acute-phase reaction. Subsequently, studies will be undertaken to determine whether identified extra-PO, IL1-sensitive febrigenic sites similarly can drive the nonfebrile APR, and whether they do so through the same transmitters as the PO. The results should permit differentiating among responses that might be activated by IL1 at different loci within the brain and provide information toward understanding the mode of action of IL1 in the induction of fever and other acute-phase host defense responses.

受感染的成年人除了发烧外，还表现出典型的 非特异性宿主反应的串联，称为急性期 反应(APR)。这些包括：中性粒细胞增多症， 某些血浆蛋白和微量金属的浓度，以及各种 其他相关调整。很久以来，人们就知道 感染是由巨噬细胞/单核细胞的内源性因子介导的， 被称为白介素I(IL1)。在过去的十年里，有证据表明 累积表明APR的非热分量也是 由IL1介导。这是公认的主要地点的 IL1的发热作用是下丘脑视前区(PO)。 可导致发烧的辅助IL1敏感部位已被本地化 外侧下丘脑、脑桥和延髓。我的最新结果 实验室表明，PO也参与了 某些非热性急性时相反应对IL_1、In的调节 尤其是肝脏糖蛋白的合成。这些数据还包括 提示激活发热和非发热的视前单位 对IL1的反应可能是不同的。因此，这些拟议的研究是 旨在进一步分析PO调解中的神经系统 急性期反应。具体地说，它们旨在确定 无论是单胺和阿片类药物，这两类神经化学物质 可能在发热产生中起作用的物质也可能是 与控制非热的急性期反应有关。 随后，将进行研究，以确定是否已确定 额外的PO，IL1敏感的发烧部位同样可以驱动非发烧 APR，以及它们是否通过与PO相同的发射器完成此操作。这个 结果应该允许区分可能是 由IL1在大脑中的不同位置激活，并提供信息 了解IL-1在致热中的作用方式 和其他急性期宿主防御反应。