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New concepts on the pathogenesis of fever.

Abstract
For more than 50 years, experimental studies on fever have focused on a substance from leukocytes called leukocytic or endogenous pyrogen. Various investigators concluded that changes associated with infection--such as numbers of circulating leukocytes; levels of trace metals, amino acids, and hepatic proteins; and altered lymphocyte function--were also caused by endogenous leukocyte mediators. There was reasonable evidence that fever and these other changes were brought about through the action of a single endogenous pyrogen, now known as interleukin 1 (IL-1). Two forms of IL-1 have been cloned (IL-1 beta and IL-1 alpha), and studies of recombinant IL-1 preparations have confirmed that fever and the broad spectrum of host responses to infection and injury are indeed mediated by this substance. However, IL-1 is not the only leukocyte product that induces fever: tumor necrosis factor (cachectin) and interferon produce fever in humans and animals. Accordingly, the concept of a single endogenous pyrogen now requires modification. Nature has conferred the ability to produce fever on no fewer than three structurally distinct molecules. Investigators trying to determine what triggers the hypothalamus to initiate fever in a particular disease must now consider these three endogenous pyrogens, either alone or together, as mediators of fever.
AuthorsC A Dinarello, J G Cannon, S M Wolff
JournalReviews of infectious diseases (Rev Infect Dis) 1988 Jan-Feb Vol. 10 Issue 1 Pg. 168-89 ISSN: 0162-0886 [Print] United States
PMID2451266 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)
Chemical References
  • Interleukin-1
  • Interleukin-2
  • Prostaglandins
  • Pyrogens
  • Tumor Necrosis Factor-alpha
  • Interferons
Topics
  • Acute-Phase Reaction (etiology)
  • Animals
  • Endothelium (metabolism)
  • Fever (etiology)
  • Humans
  • Hypothalamus (metabolism)
  • Interferons (metabolism)
  • Interleukin-1 (biosynthesis, metabolism)
  • Interleukin-2 (metabolism)
  • Prostaglandins (biosynthesis)
  • Pyrogens (metabolism)
  • Tumor Necrosis Factor-alpha (metabolism)

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