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Protection against lipopolysaccharide-induced death by fluoroquinolones
A A Khan1, T R Slifer, F G Araujo
1Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, Palo Alto, California 94301, USA.
Antimicrobial Agents and Chemotherapy
|October 19, 2000
Summary
Fluoroquinolones, antibiotics with immunomodulatory effects, significantly improved survival rates in mice challenged with lipopolysaccharide (LPS). These drugs also reduced key inflammatory cytokines, suggesting potential therapeutic benefits for sepsis.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Fluoroquinolones possess immunomodulatory properties affecting cytokine production in human monocytes.
- Lipopolysaccharide (LPS) is a potent endotoxin that can induce a lethal inflammatory response.
Purpose of the Study:
- To investigate the protective effects of fluoroquinolones against lethal doses of LPS in a mouse model.
- To determine the impact of fluoroquinolones on serum cytokine levels in LPS-treated mice.
Main Methods:
- Administration of lethal doses of LPS to mice.
- Treatment with specific fluoroquinolones: trovafloxacin, ciprofloxacin, and tosufloxacin.
- Monitoring survival rates and measuring serum levels of interleukin-6 and tumor necrosis factor alpha.
Main Results:
- Trovafloxacin (100 mg/kg) demonstrated significant protection (75% survival), while tosufloxacin (100 mg/kg) and ciprofloxacin (250 mg/kg) offered 50% and 25% protection, respectively.
- Fluoroquinolone treatment significantly reduced serum levels of interleukin-6 and tumor necrosis factor alpha in LPS-exposed mice.
- Statistical significance (P < 0.002) was observed for all protective effects and cytokine reductions.
Conclusions:
- Fluoroquinolones exhibit a dose-dependent protective effect against lethal LPS challenge in mice.
- The reduction in pro-inflammatory cytokines (IL-6, TNF-alpha) likely mediates the observed survival benefits.
- These findings suggest a potential therapeutic role for fluoroquinolones in managing LPS-induced shock and sepsis in humans.