The sensitivity of LPS tolerance mice to Escherichia coli is mediated through modulation of pro-inflammatory cytokine release

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 1mg/kg LPS for 5days and then intravenously injected with 50 mg/kg LPS on the sixth day to establish LPS tolerance mice model.In this model,the seven daysu0027 survival rate was observed or serum TNF-α,IL-6levels at 6h,12 h after injection of 50mg/kg LPS were detected by ELISA assay.Then different concentration of E.coli were intraperitoneally administrated,the seven daysu0027 survival rate was observed,bacterialloads in blood were counted and serum TNF-α,IL-6levels were detected.RESULTS:The survival rate of 50 mg/kg LPS attack group was0%,however,the survival rate of LPS tolerance mice was 100%.The serum TNF-αand IL-6levels in LPS tolerance group were obviously lower than those of 50mg/kg LPS attack group(P0.01).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 5.0×108CFU/kg of E.coli.The blood bacterial load of LPS tolerance mice suffered fromE.coli hit was much higher than that of only E.coli attack mice(P0.01).The serum TNF-αand IL-6levels were much lower in LPS tolerance mice suffered with E.coli hit compared to only E.coli attack mice(P0.01).CONCLUSION:LPS tolerancemice model could be successfully established by intraperitoneal injection of 1 mg/kg LPS for 5consecutive days and then intravenous injection of 50mg/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 bodyu0027s resistance.