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Investigating the hypothermic effects of fluoroquinolone antimicrobials on non-bacterial fever model mice
Ryohei Hara1, Kazuaki Taguchi2, Hiromi Ogino3
1Division of Pharmacodynamics, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-Ku, Tokyo, 105-8512, Japan.
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.
Insights
Fluoroquinolone antimicrobials like ciprofloxacin, gatifloxacin, and levofloxacin can lower body temperature. This hypothermic effect, potentially mediated by glucocorticoids, may contribute to their fever-reducing properties.
Area of Science:
- Pharmacology
- Thermoregulation
- Infectious Disease
Background:
- Fluoroquinolones (FQ) exhibit antipyretic effects in bacterial infections.
- The precise mechanism behind FQ antipyresis is unclear, with potential roles for antimicrobial activity or direct hypothermic effects.
Purpose of the Study:
- To investigate the hypothermic effects of specific fluoroquinolones (ciprofloxacin, gatifloxacin, levofloxacin) on non-bacterial fever.
- To explore the involvement of glucocorticoids in mediating these temperature-lowering effects.
Main Methods:
- Yeast-induced fever model in mice.
- Intraperitoneal administration of ciprofloxacin, gatifloxacin, and levofloxacin.
- Measurement of rectal body temperature changes post-administration.
- Assessment of gatifloxacin's hypothermic effect with aminoglutethimide (glucocorticoid synthesis inhibitor).
Main Results:
- Fluoroquinolones induced dose-dependent decreases in rectal body temperature.
- Gatifloxacin demonstrated the most significant hypothermic effect (up to 3.4 °C).
- Pre-treatment with aminoglutethimide attenuated the hypothermic effect of gatifloxacin, indicating glucocorticoid involvement.
Conclusions:
- The observed antipyretic effects of certain fluoroquinolones may be linked to their direct hypothermic actions.
- Glucocorticoid-mediated pathways appear to play a role in the hypothermic effects of these antimicrobials.
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01:29Decreased Body Temperature