Abstract A short summary of some aspects of the history of clinical fever is presented with special reference to its association with inflammation. Clinical diseases are tabulated within various broad categories and discussed in relation to the frequency with which they are associated with fever and the probable pathogenetic mechanisms involved. Certain unresolved discrepancies are emphasized in the light of our present knowledge. Title Molecular basis of fever in humans. 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.