EP fails to increase the survival rate in the CLP-induced sepsis model of HO-1−/− mice. BALB/c WT (n=12) and HO-1−/− mice (n=12) were subjected to CLP with EP (n=6, 40 mg/kg i.p.) or an equal volume of vehicle (n=6, saline) treatment at 0 and 24 h, after onset of sepsis. Survival was monitored daily for up to 5 days (A). To determine serum HMGB1 levels, WT and HO-1−/− mice were treated with EP (40 mg/kg i.p., n=5) or an equal volume of vehicle (n=4, saline) at 0 and 12 h after onset of sepsis (CLP). Twenty-four hours later, blood was collected by cardiac puncture and subjected to HMGB1 (B) and ELISA (C) analysis. The Kaplan–Meier program was utilized to compare the differences in mortality rates between groups. **p=0.009, WT+EP versus WT+saline or HO-1−/−+EP or HO-1−/−+saline. *p=0.047, WT+saline versus
HO-1−/−+saline or HO-1−/−+EP (A). Data are presented as mean±SD of three independent experiments. In (B) and (C), significance compared to sham, **p<0.01; significance compared to CLP, †p<0.05 and ††p<0.01; significance to compared to WT+EP, §p<0.05. N.S., not significant; CLP, cecal ligation and puncture; WT, wild-type.