Artesunate interacts with Vitamin D receptor to reverse mouse model of sepsis-induced immunosuppression via enhancing autophagy

Shenglan Shang; Jiaqi Wu; Xiaoli Li; Xin Liu; Pan Li; Chunli Zheng; Yonghua Wang; Songqing Liu; Jiang Zheng; Hong Zhou

The results from CLP mice showed that AS treatment decreased the mortality of CLP mice challenged with PA from 85% to 50% (Figure 1b) , suggesting that AS could protect CLP-induced immunosuppression in mice. In CLP mice unchallenged with PA, the levels of TNF-α, IL-1β, and IL-6 were extremely low in the serum, spleen, and lungs. However, their levels increased significantly in AS-treated CLP mice (Figure 1c) . Furthermore, the cytokines levels in CLP mice challenged with PA were also much lower in contrast with sham mice challenged with PA, demonstrating that bacterial challenge could not induce pro-inflammatory cytokines release in sepsis-induced immunosuppressed mice. Importantly, AS treatment significantly augmented the cytokine levels (Figure 1d ), indicating that AS could increase cytokine levels in sepsis-induced immunosuppressed mice. Subsequently, the results showed that the bacterial loads obviously increased in the tissues of CLP mice challenged with PA compared with those in the sham mice, demonstrating that the CLP mice had a lower bacterial clearance ability. However, AS significantly decreased the bacterial load ( Figure 1e) , suggesting AS could protect sepsis-induced immunosuppression by increasing pro-inflammatory cytokine release and decreasing the bacterial load.