Interleukin-6 as an endogenous pyrogen: induction of prostaglandin E2 in brain but not in peripheral blood mononuclear cells

Charles A. Dinarello, Joseph G. Cannon, Javier Mancilla, Isis Bishai, Jodi Lees, Flavio Coceani

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Fever induced by endogenous as well as exogenous pyrogens is often prevented by cyclooxygenase inhibitors; endogenous pyrogens stimulate prostaglandin E2 (PGE2) in or near the thermoregulatory centers of the brain. The cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF), are two pyrogens which stimulate brain PGE2 formation during fever and also increase PGE2 synthesis in human mononuclear cells in vitro. In the present study, we examined whether interleukin-6 (IL-6) stimulates PGE2 formation in a manner similar to IL-1 and TNF. Both glycosylated and non-glycosylated forms of recombinant human IL-6 were tested. Following intravenous injection into rabbits, the glycosylated IL-6 was more pyrogenic than the non-glycosylated form and there was no evidence of synergy in the production of fever when IL-6 and IL-1 were given simultaneously. IL-6 fever was blocked by prior administration of the cyclooxygenase inhibitor ibuprofen. IL-6 was also pyrogenic in the cat by either the systemic or the intraventricular route. However, in both species, IL-6 was less effective than IL-1ß. When given intraventricularly to cats, IL-6 produced an increase in PGE2 levels of the cerebrospinal fluid in parallel with the rise in body temperature. In the latter respect, IL-6 imitated IL-1ß; however, IL-6 from 0.15-15 μg/ml did not increase mononuclear cell PGE2 production in vitro whereas IL-1ß induced 20-30-fold increases in PGE2 at 100 ng/ml. These results suggest that IL-6, similar to IL-1 and TNF, causes fever via the rapid increase in brain PGE2 synthesis but unlike IL-1, stimulation of PGE2 in mononuclear cells was not observed by IL-6.

Original languageEnglish (US)
Pages (from-to)199-206
Number of pages8
JournalBrain Research
Issue number2
StatePublished - Oct 25 1991
Externally publishedYes


  • Endotoxin
  • Fever mechanism
  • Interleukin-1
  • Interleukin-6

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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