Investigating the hypothermic effects of fluoroquinolone antimicrobials on non-bacterial fever model mice

Abstract

Background: Fluoroquinolone (FQ) antimicrobials have antipyretic effects during the treatment of bacterial infections; however, it is not clear whether these are due to their antimicrobial activities or their hypothermic effects. In this study, we investigated the hypothermic effects of FQ antimicrobials (ciprofloxacin [CPFX], gatifloxacin [GFLX], and levofloxacin [LVFX]) on fever by evaluating rectal body temperature changes in a mouse model of non-bacterial fever.

Methods: CPFX, GFLX, and LVFX were administered intraperitoneally to non-bacterial fever model mice induced by yeast. Rectal body temperature was measured up to 180 min after administration.

Results: A decrease in rectal body temperature of up to 1.2 °C for CPFX, 3.4 °C for GFLX, and 1.0 °C for LVFX was observed. The decrease in temperature was induced by an increase in the plasma concentration of FQ antimicrobials, suggesting that they are responsible for the temperature reduction. Focusing on glucocorticoids, one thermoregulation mechanism, we investigated the substances responsible for the reduction in rectal body temperature induced by FQ antimicrobials. Aminoglutethimide (an inhibitor of glucocorticoid production) were premedicated, followed by intraperitoneal administration of GFLX in the yeast-induced fever mouse model, resulting in attenuated GFLX-induced hypothermic effects.

Conclusions: These results suggest that certain antipyretic effects of CPFX, GFPX, and LVFX during fever may contribute to their hypothermic effects; certain mechanisms are glucocorticoid-mediated.

Keywords: Fever; Fluoroquinolone; Glucocorticoid; Hypothermia; Mice.

Fig. 1

Rectal body temperature changes over time following intraperitoneal administration of ciprofloxacin, gatifloxacin, and levofloxacin at 100 mg/kg in yeast-induced fever model mice. Each point represents the mean ± S.E. of the change in rectal body temperature from baseline in each mouse (n = 3). Significant differences were determined using Dunnett's multiple comparison test. **p < 0.01 vs. 0 min of each fluoroquinolone antimicrobial

Fig. 2

Plasma concentrations of a ciprofloxacin (CPFX), b gatifloxacin (GFLX), and c levofloxacin (LVFX) administered intraperitoneally at 100 mg/kg in yeast-induced fever model mice. Each point represents the mean blood concentration of fluoroquinolone antimicrobials in each mouse ± S.E. (n = 3). Dotted line: rectal body temperature changes over time, shown in Fig. 1

Fig. 3

Rectal body temperature changes over time following intraperitoneal administration of gatifloxacin (GFLX) in yeast-induced fever model mice pre-administered aminoglutethimide (AMG). Each point is the mean ± S.E. of the change in rectal body temperature from baseline in each mouse (n = 3–5). Statistical differences were assessed by one-way ANOVA followed by the Bonferroni test. **p < 0.01 vs. control. # p < 0.05 vs. GFLX. †p < 0.05, †† < 0.01 vs. AMG. Changes in rectal body temperature over time for GFLX are shown in Fig. 1