Protection against lipopolysaccharide-induced death by fluoroquinolones

Abstract

Because fluoroquinolones have an immunomodulatory effect on cytokine production by lipopolysaccharide (LPS)-treated human monocytes, we examined the effect of fluoroquinolones on the survival of mice injected with a lethal dose of LPS. Trovafloxacin (100 mg/kg), ciprofloxacin (250 mg/kg), and tosufloxacin (100 mg/kg) protected 75% (P = 0.0001), 25% (P = 0.002), and 50% (P = 0.002), respectively, of mice against death. The fluoroquinolones significantly reduced serum levels of interleukin-6 and tumor necrosis factor alpha in LPS-treated mice. The protective effects of fluoroquinolones in LPS-induced shock in mice may also occur in humans.

FIG. 1

Survival in SW mice treated orally with 100 mg of trovafloxacin per kg and injected i.v. with 1,000 μg of LPS 1 h later (A) or treated orally with 250 mg of ciprofloxacin per kg and injected with LPS 1 h later (B). The P values, as determined by Kaplan-Meier product limited-survival analysis, were 0.001 for trovafloxacin and 0.008 for ciprofloxacin.

FIG. 2

Levels of serum cytokines in mice treated orally with 100 mg of trovafloxacin per kg and injected i.v. with 1,000 μg of LPS at 1 h (A) and 4 h (B) after injection. ∗, P values of ≤0.05 compared with LPS alone.

FIG. 3

Levels of serum cytokines in mice treated orally with 100 mg of ciprofloxacin per kg and injected i.v. with 1,000 μg of LPS at 1 h (A) and 4 h (B) after injection. ∗, P values of ≤0.05 compared with LPS alone.