Characteristics of thermoregulatory and febrile responses in mice deficient in prostaglandin EP1 and EP3 receptors

Previous studies have disagreed about whether prostaglandin EP1 or EP3 receptors are critical for producing febrile responses. We therefore injected lipopolysaccharide (LPS) at a variety doses (1 mug kg(-1)-1 mg kg(-1)) intraperitoneally (I.P.) into wild-type (WT) mice and mice lacking the EP1 or the Ep(3) receptors and measured changes in core temperature (T-c) by using telemetry. In WT mice, I.P. injection of LPS at 10 mug kg(-1) increased T-c about 1degreesC, peaking 2 h after injection. At 100 mug kg(-1), LPS increased T-c, peaking 5-8 h after injection. LPS at 1 mg kg(-1) decreased T-c, reaching a nadir at 5-8 h after injection. In EP1 receptor knockout (KO) mice injected with 10 mug kg(-1) LPS, only the initial (< 40 min) increase in T-c was lacking; with 100 mug kg(-1) LPS the mice showed no febrile response. In EP3 receptor KO mice, LPS decreased T-c in a dose- and time-dependent manner. Furthermore, in EP3 receptor KO mice subcutaneous injection of turpentine did not induce fever. Both EP1 and EP3 receptor KO mice showed a normal circadian cycle of T-c and brief hyperthermia following psychological stress (cage-exchange stress and buddy-removal stress). The present study suggests that both the EP1 and the EP3 receptors play a role in fever induced by systemic inflammation but neither EP receptor is involved in the circadian rise in T-c or psychological stress-induced hyperthermia in mice.