CENTRAL MONOAMINES AND OPIOIDS IN ACUTE-PHASE REACTION

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：嗜中性白细胞增多， 某些血浆蛋白和微量金属的浓度，以及各种 其他相关调整。 人们早就知道， 感染由来自巨噬细胞/单核细胞的内源性因子介导， 称为白细胞介素I（IL 1）。 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IL 1介导。 众所周知， IL 1的发热作用是下丘脑的视前区（PO）。 辅助IL-1敏感的网站，可以驱动发热已定位在 外侧下丘脑脑桥和延髓 最近的结果从我的 实验室表明，PO也参与了重要的 调节对IL 1的某些非热急性期反应， 特别是糖蛋白的肝合成。 所述数据进一步 表明激活发热和非发热的视前单位 对IL 1的反应可能不同。 因此，这些拟议的研究是 旨在进一步分析PO介导的神经系统 急性期反应 具体来说，它们旨在确定 无论是单胺类物质还是阿片类物质， 可能在发热过程中起作用的物质，也可能是 涉及非热急相反应的控制。 随后，将进行研究，以确定是否发现 PO外，IL 1敏感的发热部位同样可以驱动非发热性 APR，以及他们是否通过与PO相同的发射机这样做。 的 结果应允许区分可能 在大脑内的不同位点被IL 1激活，并提供信息 了解IL-1在发热诱导中的作用方式 和其他急性期宿主防御反应。

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.