Expanding the febrigenic role of cyclooxygenase-2 to the previously overlooked responses.
Previous studies on the role of cyclooxygenase (COX)-1 and -2 in fever induced by intravenous LPS have failed to investigate the role of these isoenzymes in the earliest responses: monophasic fever (response to a low, near-threshold dose of LPS) and the first phase of polyphasic fever (response to higher doses). We studied these responses in 96 mice that were COX-1 or COX-2 deficient (-/-) or sufficient (+/+). Each mouse was implanted with a temperature telemetry probe into the peritoneal cavity and a jugular catheter. The study was conducted at a tightly controlled, neutral ambient temperature (31 degrees C). To avoid stress hyperthermia (which masks the onset of fever), all injections were performed through a catheter extension. The +/+ mice responded to intravenous saline with no change in deep body temperature. To a low dose of LPS (1 microg/kg iv), they responded with a monophasic fever. To a higher dose (56 microg/kg), they responded with a polyphasic fever. Neither monophasic fever nor the first phase of polyphasic fever was attenuated in the COX-1 -/- mice, but both responses were absent in the COX-2 -/- mice. The second and third phases of polyphasic fever were also missing in the COX-2 -/- mice. The present study identifies a new, critical role for COX-2 in the mediation of the earliest responses to intravenous LPS: monophasic fever and the first phase of polyphasic fever. It also suggests that no product of the COX-1 gene, including the splice variant COX-1b (COX-3), is essential for these responses.
Steiner
Alexandre A
AA
Systemic Inflammation Laboratory, Trauma Research, St. Joseph's Hospital and Medical Center, 350 W. Thomas Rd., Phoenix, Arizona 85013, USA.
Rudaya
Alla Y
AY
Robbins
Jared R
JR
Dragic
Alexander S
AS
Langenbach
Robert
R
Romanovsky
Andrej A
AA
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced / Q000201:enzymology*; D006579:Heterozygote; D006720:Homozygote; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013686:Telemetry
D008070:Lipopolysaccharides