Tanshinone IIA attenuates sepsis-induced immunosuppression and improves survival rate in a mice peritonitis model

The importance of sepsis-induced immunosuppression and its contribution to mortality has recently emerged. In this study we examined the effects of Tanshinone II-A (TSN), a widely used traditional Chinese medicine, on immunosuppression in experimental peritonitis induced septic mice. Sepsis was achieved by means of cecal ligation and puncture (CLP). TSN at different doses (5, 15 and 45 mg/kg, i.p.) were used at different time-points (0, 3, 6 and 12 h) after CLP to evaluate its effect on the survival of septic mice. In parallel experiments, mice given TSN at optimal dose and time-point were euthanized to collect peritoneal macrophages, blood and tissue samples at 24 h after the CLP. TSN improved the survival of septic mice in a dose- and time-dependent manner. TSN reduced CLP-induced serum biochemical parameters and protected organs from histopathological injuries. CLP-induced apoptosis and decreased percentages of splenic CD4+ and CD8+ T cells were reversed in TSN-treated mice. Moreover, CLP-induced formation of regulatory T cells (Treg) in the spleen was abolished in TSN-treated mice. CLP greatly decreased the levels of interferon-γ and interleukin (IL)-2 in the spleen, while the levels of IL-4 and IL-10 increased after CLP. TSN completely reversed these alterations and elicited a more-balanced Th1/Th2 response. Moreover, TSN promoted macrophage phagocytotic activity and improved bacterial clearance of septic mice. Lastly, TSN abolished CLP-triggered increase in serum HMBG1 level. And HMGB1 neutralization could increase the percentages of splenic CD3+CD4+/CD3+CD8+ lymphocytes and decreased the Treg population. Overall, our data suggest that TSN exerts immune modulatory effect and might be a useful strategy to ameliorate immunosuppression in polymicrobial sepsis.