Ogino Hiromi, Fujii Miho, Ono Mariko, Maezawa Kayoko, Hori Seiji, Kizu Junko
Department of Practical Pharmacy, Keio University Faculty of Pharmacy, Tokyo, Japan.
J Infect Chemother. 2009 Jun;15(3):168-73. doi: 10.1007/s10156-009-0680-1. Epub 2009 Jun 25.
Fluoroquinolones have been reported to affect cytokine production in vitro. We investigated the effects of fluoroquinolones on lipopolysaccharide (LPS)-induced inflammatory cytokine production in vivo and in vitro. LPS was administered to mice treated with ciprofloxacin, gatifloxacin, norfloxacin, and levofloxacin, and the serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), and interleukin 6 (IL-6) were measured. In addition, peritoneal macrophages collected from mice were treated with the four fluoroquinolones for 1 h, followed by the addition of LPS, and the TNF-alpha, IL-1beta, and IL-6 levels in culture fluid were measured. In LPS-treated mice, ciprofloxacin, gatifloxacin, and norfloxacin (100 mg/kg) significantly reduced the serum TNF-alpha level (6.8%-63.6% of control). Levofloxacin at 100 mg/kg did not affect the TNF-alpha level, whereas levofloxacin at a lower dose (10 mg/kg) significantly increased the level. All four fluoroquinolones (100 mg/kg) investigated in this study tended to decrease the serum IL-1beta levels (65.5%-65.9% of control), but this was not a significant change. The serum IL-6 levels were increased in ciprofloxacin-administered mice, whereas the other fluoroquinolones did not affect the serum IL-6 levels. In mouse peritoneal macrophages, LPS induced TNF-alpha, IL-1beta, and IL-6 production. Ciprofloxacin, gatifloxacin, and norfloxacin (100 mug/ml) inhibited both TNF-alpha (12.1%-69.0% of control) and IL-1beta production (22.1%-68.8% of control). Levofloxacin (100 mug/ml) inhibited IL-1beta production (65.0% of control), but not TNF-alpha production. LPSstimulated IL-6 production was inhibited only by norfloxacin (59.5 % of control). Our in vivo and in vitro results suggest that fluoroquinolones, especially ciprofloxacin, gatifloxacin, and norfloxacin, which have a cyclopropyl group at the N1 position and/or a piperazinyl group at the C7 position, modify inflammatory responses.
据报道，氟喹诺酮类药物在体外会影响细胞因子的产生。我们研究了氟喹诺酮类药物在体内和体外对脂多糖（LPS）诱导的炎性细胞因子产生的影响。给用环丙沙星、加替沙星、诺氟沙星和左氧氟沙星治疗的小鼠注射LPS，并检测血清中肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）和白细胞介素6（IL-6）的水平。此外，从小鼠收集的腹腔巨噬细胞用这四种氟喹诺酮类药物处理1小时，然后加入LPS，并检测培养液中TNF-α、IL-1β和IL-6的水平。在LPS处理的小鼠中，环丙沙星、加替沙星和诺氟沙星（100mg/kg）显著降低血清TNF-α水平（对照组的6.8%-63.6%）。100mg/kg的左氧氟沙星不影响TNF-α水平，而较低剂量（10mg/kg）的左氧氟沙星则显著提高该水平。本研究中所研究的所有四种氟喹诺酮类药物（100mg/kg）都倾向于降低血清IL-1β水平（对照组的65.5%-65.9%），但这并非显著变化。环丙沙星给药的小鼠血清IL-6水平升高，而其他氟喹诺酮类药物不影响血清IL-6水平。在小鼠腹腔巨噬细胞中，LPS诱导TNF-α、IL-1β和IL-6的产生。环丙沙星、加替沙星和诺氟沙星（100μg/ml）抑制TNF-α（对照组的12.1%-69.0%）和IL-1β的产生（对照组的22.1%-68.8%）。左氧氟沙星（100μg/ml）抑制IL-1β的产生（对照组的65.0%），但不抑制TNF-α的产生。LPS刺激的IL-6产生仅被诺氟沙星抑制（对照组的59.5%）。我们的体内和体外结果表明，氟喹诺酮类药物，尤其是在N1位有环丙基和/或在C7位有哌嗪基的环丙沙星、加替沙星和诺氟沙星，会改变炎症反应。
