Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Inflammation. 2018 Jun;41(3):1008-1020. doi: 10.1007/s10753-018-0754-2.
Due to the imbalance between hyper-inflammation and hypo-inflammation, which are characterized by excessive cytokine productions and programmed death 1 (PD-1) upregulation, respectively, sepsis remains a highly lethal inflammatory syndrome with limited effective therapies. Mycophenolate mofetil (MMF), an immunosuppressant, has been reported to attenuate various inflammatory diseases. However, the role of MMF in sepsis therapy remains to be elucidated. C57BL-6J mice underwent cecal ligation and puncture (CLP) and were treated either with or without MMF. Survival rate and organ injuries were compared. Cytokine levels, bacteria clearance, apoptosis of spleen and peritoneal macrophages, and PD-1 expression were assessed. At the beginning of CLP, 60 mg/kg MMF administered by gavage significantly protected septic mice, which was evidenced by improved survival and attenuated organ injuries, decreased cytokines, lower bacterial loads, and alleviated immune cell apoptosis. In addition, immune cells in the MMF mice showed lower PD-1 expression and improved immune response to pathogeny stimuli. MMF protects septic mice via the dual inhibition of cytokine releasing and PD-1 expression.
由于过度炎症和低炎症之间的失衡，分别表现为过度细胞因子产生和程序性死亡 1 (PD-1)上调，脓毒症仍然是一种高度致命的炎症综合征，治疗方法有限。霉酚酸酯（MMF），一种免疫抑制剂，已被报道可减轻各种炎症性疾病。然而，MMF 在脓毒症治疗中的作用仍有待阐明。C57BL-6J 小鼠接受盲肠结扎和穿刺（CLP），并分别用或不用 MMF 治疗。比较存活率和器官损伤。评估细胞因子水平、细菌清除、脾和腹膜巨噬细胞凋亡以及 PD-1 表达。在 CLP 开始时，通过灌胃给予 60mg/kg 的 MMF 可显著保护脓毒症小鼠，这表现在存活率提高和器官损伤减轻、细胞因子减少、细菌负荷降低以及免疫细胞凋亡减轻。此外，MMF 小鼠中的免疫细胞表现出较低的 PD-1 表达和对病原体刺激的改善免疫反应。MMF 通过双重抑制细胞因子释放和 PD-1 表达来保护脓毒症小鼠。
