Prophylactic simvastatin treatment modulates the immune response and increases survival of mice following induction of lethal sepsis

OBJECTIVE: To investigate whether and how simvastatin mediates protection from lethal sepsis, using a mouse model. METHODS: Sixty C57BL/6 mice were selected and divided into three groups (“control,” “model,” and “observation”; n = 20 mice per group). Mice in the model and observation groups underwent cecal ligation and puncture; mice in the observation group received simvastatin. After 24 hours of induced sepsis, serum concentrations of IL-6, TNF-α, IL-1, and IL-10 were measured by ELISA. Serum malondialdehyde (MDA) concentrations and serum superoxide dismutase (SOD) activities were quantified by radioimmunoassay. RESULTS: The mean duration of survival of mice in the observation group was significantly longer than that of the model group. The serum concentrations of IL-6, TNF-α, IL-1, IL-10, and MDA were significantly higher in the observation group than in the control group. Serum SOD activities were significantly lower in the observation group than in the control group. CONCLUSIONS: Simvastatin can alleviate symptoms of sepsis in mice and improve their rates of survival. The mechanism of action of simvastatin may be mediated by inhibition of the systemic inflammatory response and oxidative stress.