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Effects of quinolones on granulocyte function in vitro

Einfluß von Chinolonen auf Granulozytenfunktionen in vitro

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Summary

Granulocytes (PMN) play an important role in antibacterial host defence. The modulation of PMN-function by different antibiotics has been shown previously. Therefore, we investigated the possible immuno-modulatory effects of four new quinolone antibiotics: ciprofloxacin, norfloxacin, pefloxacin, ofloxacin. Pure PMN-preparations were obtained from healthy volunteers and incubated for 30 min at 37° C with the different quinolones at different concentrations (0.1-1-5-10 mg/l). A complete PMN-functional profile was assayed. At all concentrations tested no significant differences were seen for myeloperoxydase content, superoxide production and chemiluminescence. A significant stimulation of phagocytosis and killing occurred at 10 mg/l of norfloxacin and at 10 mg/l of pefloxacin. An increase of chemotaxis towards formyl-methionyl-leucyl-phenylalanin was noted at 10 mg/l of ofloxacin, while stimulation of hexose monophosphate shunt was seen at 1 mg/l of ciprofloxacin and 10 mg/l of ofloxacin. The mechanism whereby both subinhibitory and inhibitory concentrations of quinolones moderately influence PMN-responsiveness is not yet known. Further studies are needed to elucidate the nature of this quinolone-effect and to assess its relevancein vivo.

Zusammenfassung

Granulozyten sind entscheidend an der antibakteriellen Abwehr beteiligt. Bereits in früheren Untersuchungen wurde gezeigt, daß verschiedene Antibiotika die Granulozytenfunktionen modulieren. Wir haben daher vier neue Chinolon-Antibiotika, Ciprofloxacin, Norfloxacin, Pefloxacin und Ofloxacin, im Hinblick auf mögliche immunmodulierende Eigenschaften untersucht. Reine Granulozytenpräparationen wurden von gesunden freiwilligen Probanden gewonnen. Sie wurden 30 Minuten lang bei 37° C mit verschiedenen Konzentrationen (0,1-1-5-10 mg/l) der genannten Chinolone inkubiert. Es wurde ein komplettes Granulozyten-Funktionsprofil erstellt. Bei den geprüften Konzentrationen waren keine signifikanten Veränderungen im Myeloperoxy-dasegehalt, der Superoxidbildung und Chemilumineszenz festzustellen. Bei der Inkubation mit 10 mg/l Norfloxacin und 10 mg/l Pefloxacin fand sich eine signifikante Stimulierung der Phagozytose und bakteriellen Abtötung. Bei einer Konzentration von 10 mg/l Ofloxacin war eine Zunahme der Chemotaxis gegenüber Formyl-methionyl-leucyl-phenylalanin festzustellen. Bei Inkubation mit 1 mg/l Ciprofloxacin und 10 mg/l Ofloxacin wurde eine Stimulation des Hexose-Monophosphat-Shunts beobachtet. Der Wirkungsmechanismus dieser mäßig ausgeprägten Veränderungen der Granulozyten-Reaktivität unter dem Einfluß von subinhibitorischen und inhibitorischen Konzentrationen von Chinolonen ist noch unbekannt. Für die Charakterisierung dieses Chinoloneffektes und die Beurteilung seinerIn-vivo-Relevanz sind weitere Untersuchungen nötig.

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Boogaerts, M.A., Malbrain, S., Scheers, W. et al. Effects of quinolones on granulocyte function in vitro. Infection 14, S258–S262 (1986). https://doi.org/10.1007/BF01661288

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Keywords

  • Ofloxacin
  • Quinolones
  • Hexose
  • Norfloxacin
  • Pefloxacin