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

• DOI: 10.1152/ajpregu.1997.272.6.r1712
• Publication Date: 2017-12-25T00:02:10Z
• Authors: C. Cao; K. Matsumura; K. Yamagata; Y. Watanabe
• Keywords: Lipopolysaccharides; Male; 0301 basic medicine; Sulfonamides; Cyclooxygenase 2 Inhibitors; Fever; Brain; Analgesics, Non-Narcotic; Body Temperature; Rats; 3. Good health; Isoenzymes; 03 medical and health sciences; Cyclooxygenase 2; Prostaglandin-Endoperoxide Synthases; Abdomen; Animals; Blood Vessels; Anesthesia; Cyclooxygenase Inhibitors; RNA, Messenger; Rats, Wistar; Nitrobenzenes

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.