Nemonoxacin is a novel non-fluorinated quinolone. The effect of nemonoxacin on modulation of host immune response is not known. We sought to determine whether nemonoxacin has immunoprotective effects on lipopolysaccharide (LPS)-induced mouse sepsis model. Therefore, mice were challenged with lethal dose LPS (12.5 mg/kg) only or LPS with multi-dose nemonoxacin (40 mg/kg q12h) by intraperitoneal injection, and the results showed nemonoxacin could significantly reduce mortality from 80 to 30% in this model. The effect of nemonoxacin on immune cells in vivo and in vitro was also investigated. Mice were treated with sublethal LPS (5 mg/kg) or LPS + nemonoxacin, the myeloid cell subsets in mouse spleen were analyzed by flow cytometry, and cytokines in mouse serum were measured by ELISA. Additionally, mouse macrophage RAW264.7 cells were treated with LPS or LPS + nemonoxacin to investigate the immune modulatory effect of nemonoxacin in vitro, and the level of cytokines in cell culture supernatant was determined by ELISA. Analysis of myeloid cell subsets in the spleen showed nemonoxacin pretreatment could significantly inhibit LPS-induced proliferation of macrophages and dendritic cells but have no effect on neutrophils. Nemonoxacin could significantly reduce the expression of pro-inflammatory cytokines IL-6 and TNF-α while increase anti-inflammatory cytokine IL-10 expression, which were induced by LPS in vivo and in vitro. Finally, the immunomodulation of nemonoxacin in macrophage phagocytosis was also examined. The results displayed nemonoxacin pretreatment could significantly enhance the phagocytic function of macrophage. In conclusion, nemonoxacin has immune modulatory and protective effect on LPS-induced inflammation in vivo and in vitro.

奈莫沙星是一种新型非氟化喹诺酮类药物。奈莫沙星对调节宿主免疫反应的作用尚不清楚。我们试图确定奈莫沙星是否对脂多糖 (LPS) 诱导的小鼠脓毒症模型具有免疫保护作用。因此，小鼠仅用致死剂量 LPS（12.5 mg/kg）或 LPS 与多剂量奈莫沙星（40 mg/kg q12h）腹腔注射，结果表明奈莫沙星可以显着降低死亡率，从 80% 到 30%模型。奈莫沙星对体内外免疫细胞的影响也被调查了。用亚致死LPS（5mg/kg）或LPS+奈莫沙星处理小鼠，通过流式细胞术分析小鼠脾脏中的髓细胞亚群，并通过ELISA测量小鼠血清中的细胞因子。此外，用LPS或LPS + 奈莫沙星处理小鼠巨噬细胞RAW264.7细胞以研究奈莫沙星的体外免疫调节作用，并通过ELISA测定细胞培养上清液中细胞因子的水平。脾脏髓系细胞亚群分析表明，奈莫沙星预处理可显着抑制 LPS 诱导的巨噬细胞和树突状细胞增殖，但对中性粒细胞无影响。奈莫沙星可显着降低促炎细胞因子 IL-6 和 TNF-α 的表达，同时增加 LPS在体内和体外诱导的抗炎细胞因子 IL-10 的表达. 最后，还检查了奈莫沙星在巨噬细胞吞噬作用中的免疫调节作用。结果表明，奈莫沙星预处理可显着增强巨噬细胞的吞噬功能。总之，奈莫沙星在体内外对LPS诱导的炎症具有​​免疫调节和保护作用。