The pathogenesis of fever and its therapeutic implications

S. Pece, G. Giuliani, D. Caccavo, S. Antonaci, E. Jirillo

Research output: Contribution to journalArticlepeer-review


Physiologically, body temperature is adjusted to about 37°C and fever represents an elevation of this basal temperature above the normal range. The thermoregulatory centre located in the hypothalamus maintains physiological temperature, while fever depends on the production of exogenous pyrogens, which induce biochemical modifications in the hypothalamus. Exogenous pyrogens comprise lipopolysaccharides from Gram-negative bacteria and various toxins from Gram-positive organisms. These pyrogens can induce the release of endogenous pyrogens or cytokines (CKs), e.g. interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-α. This in turn, leads to the production of prostaglandins (PGs) of the E series. Afterwards, PGE2 provokes stimulation of the neurons localized within the hypothalamus, thereby triggering a reaction which culminates in the generation of fever. Besides bacterial infections, other conditions associated with fever, such as inflammatory bowel diseases, acquired immunodeficiency syndrome and autoimmune diseases, are characterized by the production of pyrogenic CKs. Therapeutically, besides conventional treatments of fever with antibiotics, cyclooxygenase inhibitors, non-steroidal and steroidal drugs and immunosuppressive drugs, novel therapeutic approaches are based on the experimental administration of anti-CK antibodies, IL-1 and TNF receptor antagonists and anti-inflammatory CKs (e.g. IL-10 and IL-13), respectively.

Original languageEnglish
Pages (from-to)3-7
Number of pages5
JournalMedical Science Research
Issue number1
Publication statusPublished - 1998


  • Acquired immunodeficiency syndrome
  • Acute phase response
  • Autoimmune diseases
  • Fever
  • Hypothalamus
  • Inflammatory bowel diseases
  • Lipopolysaccharides
  • Prostaglandins
  • Pyrogenic cytokines
  • Thermoregulation

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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