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

Clinical investigations have consistently shown a close correlation between Vitamin D deficiency in serum and excess mortality and morbidity, suggesting that vitamin D deficiency is tightly related to sepsis (Dickerson et al., 2016) . There are conflicting results from various studies on whether Vitamin D supplementation improves the outcome of patients with sepsis (Kearns, Alvarez, Seidel & Tangpricha, 2015; Putzu et al., 2017) . Clinical investigation on the outcome of sepsis patients accepted with Vitamin D supplementation is required in the . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https: //doi.org/10.1101 //doi.org/10. /2020 future. Considering the extensive biological effects of Vitamin D, as well as its role in maintenance of homeostasis in organisms, it is necessary to maintain the physiological concentration of Vitamin D. Based on our results, we consider that low level of Vitamin D might lead to the insufficiency of anti-inflammation response in human body, but excessive Vitamin D might induce the high level of VDR expression; however, the excessive overexpression of VDR might lead to a decreased immune function. Thus, Vitamin D supplementation is necessary in the diet but excessive intake of Vitamin D might be no benefit. Therefore, we consider that an ideal immunotherapy for sepsis is not only to exert an anti-inflammatory effect during the cytokine storm stage, but also increase the resistance to infection during the immunosuppression stage. The therapeutic effects of AS on cytokine storm stage of sepsis and its mechanism has been proved in our previous studies (Kuang et al., 2018; Li et al., 2010; Li et al., 2008) . Herein, we revealed that AS possessed therapeutic effects in sepsis-induced immunosuppression in vivo and in vitro, too.