Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 289, Issue 5, Pages R1253-R1257Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00371.2005
Keywords
prostaglandin E-2; cyclooxygenase-1b; cyclooxygenase-1V(1); cyclooxygenase-3; prostaglandin H-2 synthase; body temperature; thermoregulation; febrile phases
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Funding
- NINDS NIH HHS [R01-NS-41233] Funding Source: Medline
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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 mu g/kg iv), they responded with a monophasic fever. To a higher dose (56 mu g/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.
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