Figure 2. Temperature response and PGE2 production after casein injection into a preformed air pouch in mPGES-1 KO and chimeric mice, and treatment with cyclooxygenase inhibitor. A, Attenuated fever in mPGES-1 KO mice. *p < 0.05 and **p < 0.01 for WT mice versus mPGES-1 KO mice injected with casein (two-way ANOVA for the period of 4–10 h: F(3,30) = 17.71, p < 0.0001). B, Effect of indomethacin (Indo) injected into the air pouch (ipo) or intraperitoneally (ip). Note that both routes of administration of 10 mg/kg indomethacin abolished casein-induced fever. Injection of 1 mg/kg indomethacin into the air pouch resulted in augmented fever to casein. *p < 0.05, **p < 0.01, and ***p < 0.001 for Vehicle ipo Casein versus 10 mg/kg Indo ipo Casein, and #p < 0.05, ##p < 0.01, and ###p < 0.001 for Vehicle ipo Casein versus 1 mg/kg Indo ipo Casein (two-way ANOVA for the period of 4–10 h: F(4,51) = 17.26, p < 0.0001). C, mPGES-1 chimeric mice. WT→WT, WT mice transplanted with WT bone marrow; KO→WT, WT mice transplanted with KO bone marrow; KO→KO, KO mice transplanted with KO bone marrow; and WT→KO, KO mice transplanted with WT bone marrow. *p < 0.05, **p < 0.01, and ***p < 0.001 for KO→WT mice versus WT→KO mice injected with casein (two-way ANOVA for the period of 4–10 h: F(4,39) = 32.02, p < 0.0001). Solid lines represent mean, and dotted lines represent SEM. D, PGE2 concentration in air pouch lavage in mPGES-1 chimeric mice 5 h after casein injection into the pouch. Vehicle, mixed chimeras. Error bars represent SEM. *p = 0.0155 for WT→WT versus KO→KO and *p = 0.0358 for WT→WT versus WT→KO. ***p < 0.0001 for KO→WT versus KO→KO and WT→KO (one-way ANOVA: F(4,25) = 15.66, p < 0.0001). E, Effect of parecoxib on casein-induced fever. Parecoxib, 10 mg/kg, or saline was injected intraperitoneally 3 h after casein or vehicle injection into the air pouch (i.e., immediately before the appearance of the casein-induced fever); the temperature recordings were done 2.5 h later, close to the peak of the casein-induced fever and before the effect of parecoxib disappears (Nilsberth et al., 2009a). *p = 0.0173 for parecoxib casein versus saline casein (one-way ANOVA: F(3,20) = 4.625, p = 0.0129).