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°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 μg/kg iv), they responded with a monophasic fever. To a higher dose (56 μg/kg), they responded with a polyphasic fever. Neither monophasic fever nor the first phase of polyphasi...