First Author | Steiner AA | Year | 2005 |
Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 289 |
Issue | 5 | Pages | R1253-7 |
PubMed ID | 16081878 | Mgi Jnum | J:115450 |
Mgi Id | MGI:3691729 | Doi | 10.1152/ajpregu.00371.2005 |
Citation | Steiner AA, et al. (2005) Expanding the febrigenic role of cyclooxygenase-2 to the previously overlooked responses. Am J Physiol Regul Integr Comp Physiol 289(5):R1253-7 |
abstractText | 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. |