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[Quinolones and phagocytosis]
1Rhône-Poulenc Santé, Institut de Biopharmacie, Antony, France.
Abstract:
Fluoroquinolones as pefloxacin (PEF), ciprofloxacin (CIP), ofloxacin (OFL), norfloxacin (NOR) and enoxacin (ENO), are able to interfere with phagocyte-bacteria interaction. Active forms of PEF, CIP and OFL are concentrated in macrophages (MA) and polymorphonuclear leukocytes (PMN). These molecules appear to be free in MA cytoplasm and their release is rapid after withdrawal of extracellular antibiotic. Pretreatment of different species of bacteria (Enterobacteriaceae, S. aureus) with sub-CMIs of CIP and PEF, leads to morphologic modifications of bacteria and increases their engulfment by PMNs. Pretreatment of PMNs with therapeutic concentrations of PEF, NOR and ENO, but not CIP, increases phagocytic capacity and/or chemiluminescence. S. aureus pretreatment with sub-CMIs of CIP enhances intracellular killing. Adding of PEF after L. pneumophila phagocytosis by MA, involves a significant intracellular killing even after withdrawal of the extracellular drug. These different properties could explain good therapeutic results in severe infection treatment when the antibacterial activity of an antibiotic is not really sufficient to cure the infectious disease.
Insights
Fluoroquinolones like pefloxacin concentrate in immune cells, enhancing bacterial engulfment and killing. This explains their effectiveness in treating severe infections when other antibiotics fall short.
Area of Science:
- Pharmacology
- Immunology
- Microbiology
Context:
- Fluoroquinolones are antibiotics with known antibacterial properties.
- Their interaction with host immune cells, particularly macrophages (MA) and polymorphonuclear leukocytes (PMN), is not fully understood.
- Understanding these interactions is crucial for optimizing treatment strategies for severe infections.
Purpose:
- To investigate the effects of fluoroquinolones (pefloxacin, ciprofloxacin, ofloxacin, norfloxacin, enoxacin) on phagocyte-bacteria interactions.
- To determine how these antibiotics influence bacterial morphology, phagocytosis, and intracellular killing.
- To elucidate the mechanisms behind the therapeutic success of fluoroquinolones in complex infections.
Summary:
- Active fluoroquinolones (pefloxacin, ciprofloxacin, ofloxacin) accumulate within macrophages and PMNs.
- Sub-inhibitory concentrations of ciprofloxacin and pefloxacin alter bacterial morphology, increasing PMN engulfment.
- Pretreatment of PMNs with pefloxacin, norfloxacin, and enoxacin enhances phagocytic capacity and intracellular killing of bacteria.
Impact:
- Fluoroquinolones can enhance the host's immune response against bacterial pathogens.
- These immunomodulatory effects contribute to the efficacy of fluoroquinolones in treating severe infections.
- The findings suggest that fluoroquinolones possess dual action: direct antibacterial and host immune system enhancement.