Data Sheet 1_Irisin alleviated sepsis via enhancing macrophage phagocytosis and reducing inflammation levels.pdf

BackgroundThe treatment of sepsis relies on antibiotics following infection; however, the emergence of resistant bacteria necessitates the development of new therapeutic agents. Irisin has been shown to alleviate symptoms in septic mice, although its mechanism of action remains unclear. Our aim was to determine the mechanism by which irisin alleviates sepsis.
MethodsIn this study, septicemia was induced in mice using Escherichia coli CMCC 44102 (E) and Staphylococcus aureus CMCC 26003 (SA). The level of serum irisin were examined by ELISA kit. Mice with septicemia were intraperitoneally injected with irisin. The survival rate, body temperature, clinical manifestations, body’s bacterial load, the number of immune cells in blood, the level of inflammation in the body of the mice with septicemia were monitored to evaluate the effect of irisin therapy. The effect of irisin on the phagocytosis of spleen macrophages was observed by flow cytometry. LPS was used to induce inflammation in RAW264.7 cells and irisin was added to determine the effect of irisin on the level of macrophage inflammation.
ResultsIn vivo, sepsis decreased serum irisin levels in mice. Irisin treatment in septicemic mice enhanced the phagocytosis of splenic macrophages, improved survival rates, accelerated body temperature recovery, alleviated clinical symptoms, reduced serum and organ inflammation, lowered bacterial loads in organs and body fluids. In vitro, irisin increased phagocytosis and reduced inflammation in RAW264.7 cells.
ConclusionsIrisin improves splenic macrophage phagocytosis and reduces macrophage inflammation, thereby mitigating sepsis. Irisin holds potential as a therapeutic agent for sepsis treatment.

背景 败血症（sepsis）的临床治疗依赖于感染后使用抗生素，但耐药菌的出现促使新型治疗药物的研发迫在眉睫。已有研究表明，鸢尾素（irisin）可缓解败血症模型小鼠的症状，但其具体作用机制尚未阐明。本研究旨在明确鸢尾素缓解败血症的作用机制。
方法 本研究采用大肠杆菌（Escherichia coli）CMCC 44102（简称E株）与金黄色葡萄球菌（Staphylococcus aureus）CMCC 26003（简称SA株）构建小鼠败血症模型。采用酶联免疫吸附试验（ELISA）试剂盒检测小鼠血清鸢尾素水平。对败血症模型小鼠予以腹腔注射鸢尾素，通过监测小鼠生存率、体温变化、临床表征、体内细菌载量、血液免疫细胞数量及全身炎症水平，评估鸢尾素的治疗效果。采用流式细胞术观察鸢尾素对脾脏巨噬细胞吞噬功能的影响。以脂多糖（LPS）诱导RAW264.7细胞发生炎症反应，加入鸢尾素后检测其对巨噬细胞炎症水平的调控作用。
结果 体内实验显示，败血症可降低小鼠血清鸢尾素水平。对败血症模型小鼠予以鸢尾素干预后，可增强脾脏巨噬细胞的吞噬能力，提高小鼠生存率，加快体温恢复，缓解临床症状，减轻血清及脏器炎症反应，降低脏器与体液中的细菌载量。体外实验表明，鸢尾素可提升RAW264.7细胞的吞噬功能并降低其炎症水平。
结论 鸢尾素可增强脾脏巨噬细胞吞噬功能、抑制巨噬细胞炎症反应，从而缓解败血症进程，具备开发为败血症治疗药物的潜在价值。