Involvement of cyclooxygenase-2 in LPS-induced fever and regulation of its mRNA by LPS in the rat brain

Am J Physiol. 1997 Jun;272(6 Pt 2):R1712-25. doi: 10.1152/ajpregu.1997.272.6.R1712.

Abstract

We previously showed that a febrile dose of lipopolysaccharide (LPS) in rats resulted in induction of cyclooxygenase-2 (COX-2) mRNA in brain blood vessels/leptomeninges and telencephalic neurons. To elucidate the causal link between fever and LPS-induced COX-2 mRNA, we experimentally modified one or the other of these parameters and examined their relation. 1) LPS-induced fever was suppressed by pretreatment with a COX-2-specific inhibitor. 2) Levels of COX-2 mRNA in the neurons and blood vessels 2.5 h after LPS administration were even higher in the inhibitor-pretreated rats (afebrile) than in vehicle-pretreated ones (febrile). 3) After repeated administration of LPS, rats became tolerant to LPS, in which state LPS induced neither fever nor COX-2 mRNA in blood vessels/leptomeninges. When rats had not completely established LPS tolerance, they showed various degrees of fever that were closely correlated with the level of COX-2 mRNA in blood vessels but not with that in neurons. 4) Urethan anesthesia reduced basal as well as LPS-induced COX-2 mRNA in telencephalic neurons, but the rats still responded to LPS with fever and induction of COX-2 mRNA in the blood vessels/leptomeninges. These results suggest that COX-2 induced in brain blood vessels/leptomeninges is involved in the molecular mechanism of LPS-induced fever.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdomen
  • Analgesics, Non-Narcotic / pharmacology
  • Anesthesia
  • Animals
  • Blood Vessels / metabolism
  • Body Temperature / drug effects
  • Brain / metabolism*
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / pharmacology
  • Fever / chemically induced*
  • Fever / physiopathology
  • Isoenzymes / genetics*
  • Isoenzymes / metabolism
  • Isoenzymes / physiology*
  • Lipopolysaccharides / pharmacology*
  • Male
  • Nitrobenzenes / pharmacology
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Prostaglandin-Endoperoxide Synthases / physiology*
  • RNA, Messenger / metabolism*
  • Rats
  • Rats, Wistar
  • Sulfonamides / pharmacology
  • Tissue Distribution
  • Urethane

Substances

  • Analgesics, Non-Narcotic
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Lipopolysaccharides
  • Nitrobenzenes
  • RNA, Messenger
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Urethane
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases