Dinarello C A, Wolff S M
Am J Med. 1982 May;72(5):799-819. doi: 10.1016/0002-9343(82)90548-4.
This review presents several areas of research on the pathogenesis of fever in humans and updates new information concerning the role of fever in host defense mechanisms. Fever is mediated by a polypeptide of phagocytic cell origin called leukocytic pyrogen. Several agents and disease processes are associated with the synthesis and release of leukocytic pyrogen. Although the original studies on leukocytic pyrogen suggested that the neutrophil was the primary source, recent experiments indicate the mononuclear phagocyte to be the major producer of leukocytic pyrogen. The mechanism by which human monocytes are stimulated to produce leukocytic pyrogen is discussed, including the effects of corticosteroids, estrogens and antipyretics on the synthesis of leukocytic pyrogen in vitro. The ability of leukocytic pyrogen to alter the hypothalamic thermoregulatory center by increasing arachidonic acid metabolite levels is the most likely mechanism by which leukocytic pyrogen initiates fever. Antipyretics prevent the synthesis of certain cyclooxygenase metabolites, which accounts for their ability to reduce fever. Studies on the chemical and physical properties of human leukocytic pyrogen are reviewed and form the basis for current experiments on the similarities between leukocytic pyrogen and lymphocyte activating factor. These studies suggest that leukocytic pyrogen, in addition to producing fever, also stimulates non-hypothalamic cells involved in aspects of the acute-phase response. In this regard, leukocytic pyrogen may be an important mechanism for host defenses. Hyperthermia may also be beneficial to the host but is distinct from fever; the role of leukocytic pyrogen as well as hyperthermia as a defense mechanism is discussed.
本综述介绍了人类发热发病机制的几个研究领域，并更新了有关发热在宿主防御机制中作用的新信息。发热由一种源自吞噬细胞的多肽介导，称为白细胞致热原。几种因子和疾病过程与白细胞致热原的合成和释放有关。尽管最初关于白细胞致热原的研究表明中性粒细胞是主要来源，但最近的实验表明单核吞噬细胞是白细胞致热原的主要产生者。文中讨论了刺激人类单核细胞产生白细胞致热原的机制，包括皮质类固醇、雌激素和退热药对体外白细胞致热原合成的影响。白细胞致热原通过增加花生四烯酸代谢物水平来改变下丘脑体温调节中枢的能力，是白细胞致热原引发发热最可能的机制。退热药可阻止某些环氧化酶代谢物的合成，这解释了它们降低发热的能力。文中回顾了关于人类白细胞致热原化学和物理性质的研究，并为目前关于白细胞致热原与淋巴细胞激活因子相似性的实验奠定了基础。这些研究表明，白细胞致热原除了引起发热外，还刺激参与急性期反应的非下丘脑细胞。在这方面，白细胞致热原可能是宿主防御的重要机制。热疗对宿主也可能有益，但与发热不同；文中讨论了白细胞致热原以及热疗作为一种防御机制的作用。
