In vivo and in vitro effects of fluoroquinolones on lipopolysaccharide-induced pro-inflammatory cytokine production

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 α (TNF-α), interleukin 1β (IL-1β), 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-α, IL-1β, 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-α level (6.8%-63.6% of control). Levofloxacin at 100 mg/kg did not affect the TNF-α 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-1β 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-α, IL-1β, and IL-6 production. Ciprofloxacin, gatifloxacin, and norfloxacin (100 μg/ml) inhibited both TNF-α (12.1%-69.0% of control) and IL-1β production (22.1%-68.8% of control). Levofloxacin (100 μg/ml) inhibited IL-1β production (65.0% of control), but not TNF-α 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.