Abstract: AIM: To observe the protective effects of Artesunate (AS) on mice challenged with heat-killed escherichia coli (EC) and its inhibition on the release of cytokines induced by heat-killed EC.METHODS: A total of 48mice of Kunming species were randomly divided into six groups.EC group only received heat-killed EC at 1.2×10¹¹ CFU/kg.In AS group, AS was given by intramuscular injection at a dosage of 45 mg/kg.AS plus EC groups first received AS (5, 15, 45 mg/kg), then heatkilled EC at the same dose.AS was repeatly and intramuscularly injected at 0, 4, 24 and 48 h after heat-killed EC challenge, while the control group received only saline (NS).The mortality was observed within seven days after injection via caudal vein.In vitro, the murine peritoneal macrophages(PMφ) were pre-incubated with various concentration of AS (0.625-10 μg/mL) for 2 h, and the releases of TNF-αand IL-6 in the supernatants induced by heat-killed EC (1.25×10⁶ CFU/mL) were measured by ELISA.RESULTS: AS delayed the death time and decreased the death number of mice challenged with heatkilled EC, and the mortality decreased from 100 % to 50 %(P <0.05).In vitro, AS significantly and dosedependently inhibited the release of TNF-αand IL-6 from PMφinduced by heat-killed EC.MTT results showed AS had no significant influence on the viability of PMφwhen its concentration was under 40 μg/mL (P> 0.05). CONCLUSION: AS significantly protects on mice challenged by heat-killed EC and obviously inhibits the release of cytokines induced by heat-killed EC, suggesting that AS may be an effective drug for the sepsis.

Key words: Artesunate, heat-killed escherichia coli, murine peritoneal macrophages, TNF-α, IL-6