Forsgren A, Schlossman S F, Tedder T F
Antimicrob Agents Chemother. 1987 May;31(5):768-73. doi: 10.1128/AAC.31.5.768.
Most antibacterial agents do not affect human lymphocyte function, but a few are inhibitory. In contrast, a pronounced increase in the incorporation of [3H]thymidine in the presence of 4-quinolones was observed in these studies. The uptake of [3H]thymidine into DNA (trichloroacetic acid precipitable) was significantly increased in phytohemagglutinin-stimulated human lymphocytes when they were exposed to eight new 4-quinolone derivatives, ciprofloxacin, norfloxacin, ofloxacin, A-56619, A-56620, amifloxacin, enoxacin, and pefloxacin, at 1.6 to 6.25 micrograms/ml for 5 days. Four less antibacterially active 4-quinolones (nalidixic acid, cinoxacin, flumequine, and pipemidic acid) stimulated [3H]thymidine incorporation only at higher concentrations or not at all. Kinetic studies showed that incorporation of [3H]thymidine was not affected or slightly inhibited by ciprofloxacin 2 days after phytohemagglutinin stimulation but was increased on days 3 to 6. The total incorporation of [3H]thymidine from day 1 to day 6 after phytohemagglutinin stimulation was increased by 42 to 45% at 5 to 20 micrograms of ciprofloxacin per ml. Increased [3H]thymidine incorporation was also seen when human lymphocytes were stimulated with mitogens other than phytohemagglutinin. Ciprofloxacin added at the start of the culture had a more pronounced effect on [3H]thymidine incorporation than when added later. In spite of the apparent increase in DNA synthesis, lymphocyte growth was inhibited by 20 micrograms of ciprofloxacin per ml, and cell cycle analysis showed that ciprofloxacin inhibited progression through the cell cycle. In addition, immunoglobulin secretion by human lymphocytes stimulated by pokeweed mitogen for Epstein-Barr virus was inhibited by approximately 50% at 5 micrograms of ciprofloxacin per ml. These results suggest that the 4-quinolone drugs may also affect eucaryotic cell function in vitro, but additional studies are needed to establish an in vivo relevance.
大多数抗菌剂不会影响人类淋巴细胞功能，但有少数具有抑制作用。相比之下，在这些研究中观察到，在4-喹诺酮存在的情况下，[3H]胸苷的掺入量显著增加。当用植物血凝素刺激的人类淋巴细胞暴露于8种新的4-喹诺酮衍生物、环丙沙星、诺氟沙星、氧氟沙星、A-56619、A-56620、阿米氟沙星、依诺沙星和培氟沙星，浓度为1.6至6.25微克/毫升，持续5天时，[3H]胸苷进入DNA（可被三氯乙酸沉淀）的摄取量显著增加。四种抗菌活性较低的4-喹诺酮（萘啶酸、西诺沙星、氟甲喹和吡哌酸）仅在较高浓度下或根本不刺激[3H]胸苷的掺入。动力学研究表明，植物血凝素刺激2天后，环丙沙星对[3H]胸苷掺入没有影响或略有抑制，但在第3至6天增加。在植物血凝素刺激后第1天至第6天，每毫升5至20微克环丙沙星时，[3H]胸苷的总掺入量增加了42%至45%。当用植物血凝素以外的有丝分裂原刺激人类淋巴细胞时，也观察到[3H]胸苷掺入增加。在培养开始时添加环丙沙星对[3H]胸苷掺入的影响比稍后添加时更明显。尽管DNA合成明显增加，但每毫升20微克环丙沙星会抑制淋巴细胞生长，细胞周期分析表明环丙沙星抑制细胞周期进程。此外，每毫升5微克环丙沙星时，由商陆有丝分裂原刺激的人类淋巴细胞对爱泼斯坦-巴尔病毒的免疫球蛋白分泌被抑制约50%。这些结果表明，4-喹诺酮类药物在体外可能也会影响真核细胞功能，但需要进一步研究以确定其体内相关性。
