Abstract: AIM: To study the sensitivity of LPS tolerance mice to Escherichia coli(E.coli) and the change of its pro-inflammatory cytokines.METHODS: Mice were intraperitoneally injected 1 mg/kg LPS for 5 days and then intravenously injected with 50 mg/kg LPS on the sixth day to establish LPS tolerance mice model. In this model, the seven days' survival rate was observed or serum TNF-α, IL-6 levels at 6 h, 12 h after injection of 50 mg/kg LPS were detected by ELISA assay. Then different concentration of E.coli were intraperitoneally administrated, the seven days' survival rate was observed, bacterial loads in blood were counted and serum TNF-α, IL-6 levels were detected. RESULTS: The survival rate of 50 mg/kg LPS attack group was 0%, however, the survival rate of LPS tolerance mice was 100%. The serum TNF-α and IL-6 levels in LPS tolerance group were obviously lower than those of 50 mg/kg LPS attack group (P<0.01). Only 1.0×10⁷ CFU/kg of E.coli could lead to 100% death in LPS tolerance mice, while in normal control mice it was 5.0×10⁸ CFU/kg of E.coli . The blood bacterial load of LPS tolerance mice suffered from E.coli hit was much higher than that of only E.coli attack mice (P<0.01). The serum TNF-α and IL-6 levels were much lower in LPS tolerance mice suffered with E.coli hit compared to only E.coli attack mice (P<0.01).CONCLUSION: LPS tolerance mice model could be successfully established by intraperitoneal injection of 1 mg/kg LPS for 5 consecutive days and then intravenous injection of 50 mg/kg LPS on the sixth day. A lower concentration of E.coli could lead to LPS tolerance mice death, the results suggest that the sensitivity of LPS tolerance mice to E.coli significantly increased compared to normal mice, and the mechanism might be closely associated with the reduction of pro-inflammatory cytokine levels leading to decrease the body's resistance.

Key words: sepsis, LPS tolerance, Escherichia coli, bacterial load, pro-inflammatory cytokines