PATHOGENESIS OF FEVER IN HUMANS

发烧是由多肽的作用引起的假说 白细胞热原(LP)对体温调节系统的作用已经确立； 然而，现在有相当多的证据支持LP也 调节急性期反应的几个方面，并发挥重要的作用 在淋巴细胞功能中的作用。低密度脂蛋白的提纯及性质研究 发烧以及淋巴细胞增殖和其他生物检测 无法区分这些活动和术语白介素1(IL-1) 已经被用来表示这种活动和荷尔蒙的性质 分子。生物学上的研究仍在继续。 LP的活性和结构-功能关系。实验将会 以人单核细胞为原料大规模生产低密度脂蛋白 高效LP诱导剂毒性刺激组织细胞性淋巴瘤U937 休克毒素。脂蛋白的提纯及氨基酸序列研究 包括自大规模生产和净化计划以来 已经成立了。来自序列研究的数据对于理解 LP的性质及其对寄主的影响。利用LP的内蕴标记法 有了放射性氨基酸，净化可以被监测，而且很重要。 开始了对细胞受体的研究。Lp的特异性受体没有 已经被识别，实验被设计成使用内在标记的， 纯化的人LP以定位下丘脑中绑定LP的区域。另外， T细胞和人中性粒细胞膜泡表面受体的鉴定 将会被承担。展示LP与这些细胞和膜的结合 为受体的鉴定提供了依据。尽管不断增加 脂蛋白在急性心肌梗死几个组成部分中的作用的证据 相反应，这种分子影响许多人的机制 不同的细胞类型仍不清楚。因此，基础研究 Lp作为钙离子载体和花生四烯酸诱导剂的能力 包括酸释放。脂蛋白在人类疾病中的作用需要 体外生产和改进的生物和免疫分析方法的研究； 最近的进展为如何最好地接近检测提供了新的线索 健康和疾病期间人体体液中的系统。还包括在 这项建议是对排水中LP的回收和表征 腹膜透析患者的液体和实验以确定如何 这一过程在体内刺激LP的产生。的总体目的 这些研究旨在将LP的生产与其在各种情况下的行动联系起来 宿主组织。

The hypothesis that fever is initiated by the action of the polypeptide leukocytic pyrogen (LP) on the thermoregulatory system is well established; however, considerable evidence now supports the concept that LP also mediates several aspects of the acute phase response and plays an essential role in lymphocyte function. Purification and characterization of LP using fever as well as lymphocyte proliferation and other biological assays have been unable to separate these activities, and the term interleukin-1 (IL-1) has been adopted to denote the activity and hormonal nature of this molecule. Continued investigation is indicated on the biological activities and structure-function relationship of LP. Experiments will focus on large scale production of LP from human monocytes and the histocytic lymphoma line U937 stimulated with the potent LP-inducer, toxic shock toxin. Purification and amino acid sequence studies of LP are included since large scale production and purification schemes have been established. Data from sequence studies are vital to understanding the nature of LP and its effects on the host. Using intrinsic labeling of LP with radioactive amino acids, purification can be monitered and important studies on cell receptors initiated. Specific receptors for LP have not been identified and experiments are designed to use intrinsically labeled, purified human LP to locate areas in the hypothalamus which bind LP. Also, receptor identification on T-cells and human neutrophil membrane vesicles will be undertaken. Demonstrating LP binding to these cells and membranes provides the basis for receptor identification. Despite increasing evidence for the role of LP in mediating several components of the acute phase response, the mechanism by which this molecule affects so many different cell types remains unclear. Therefore, fundamental studies on the ability of LP to act as a calcium ionophore and inducer of arachidonic acid release are included. The role of LP in human disease requires studies on in vitro production and improved biological and immunoassays; recent progress has shed new light on how best to approach detection systems in human body fluids during health and disease. Also included in this proposal are the recovery and characterization of LP in the drainage fluid from patients on peritoneal dialysis and experiments to determine how this procedure stimulates LP production in vivo. The overall purpose of these studies is to link the production of LP to its actions on various host tissues.