Figure 4. Inhibition of COX1/2, COX2 and PGE₂-EP2 signalling decreases lung inflammation and abrogates mortality induced by a lethal dose of TsV.

(a) 129sv WT mice and Alox5^−/− mice or (b) C57BL/6 mice were treated with indomethacin (Indo; 2 mg kg⁻¹ intraperitoneally), 4 h and again 30 min before inoculation with a lethal (180 μg kg⁻¹) dose of TsV. Additional administration of vehicle or indomethacin was performed 4 and 8 h later and the survival was monitored for 8–12 h. (c) C57BL/6 mice were treated with celecoxib (5 mg kg⁻¹ intraperitoneally), or with (d) EP2 antagonist (AH6809) (5 mg kg⁻¹ intraperitoneally), 24 h and again 1 h before inoculation of 180 μg kg⁻¹ of TsV. In all experiments, TsV-inoculated mice treated with vehicle were used as controls. The lungs were excised immediately after an animal died or from mice that survived for 8–12 h; then protein content, PGE₂ release, IL-1β production, LTB₄ release and MPO activity were quantified in the lung parenchyma. The experiment was conducted once with six mice and the error bars denote s.d. *PBS versus vehicle+TsV; ^#vehicle+TsV versus Treatments+TsV; ^$PBS in 129sv WT mice versus PBS in Alox5^−/− mice; ^&Vehicle+TsV in 129sv WT mice versus Vehicle+TsV in Alox5^−/− mice. These differences were considered significant with P<0.05, according to one-way ANOVA with Bonferroni's post-test (for soluble mediators and MPO) or the log-rank test (for survival).