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The effects of ciprofloxacin on human chondrocytes in cell culture

Wirkung von Ciprofloxacin auf menschliche Chondrozyten in Kultur

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Summary

Ciprofloxacin is a highly potent antibacterial agent that is used extensively in bone and joint infections. Because of reports of potential chondro-toxicity in animals, the effects of this drug on cells derived from human cartilage were tested in liquid micromass and agarose gel cultures. An inhibition of cell proliferation as indicated by a decrease in [3H]-thymidine uptake and bromodeoxyuridine labeling at ciprofloxacin concentrations of 0.5 and 50 mg/l was found which corresponded to the therapeutic and toxic serum levels. There was no effect on proteoglycan synthesis as indicated by35SO4 incorporation. Immunocytochemistry showed no changes in morphology or staining patterns for type-I procollagen, type-II collagen, keratan sulfate and unsulfated chondroitin. Because the amount of inhibition of DNA synthesis varied with different ciprofloxacin concentrations, this data suggests that this agent has a differential effect on newly differentiating cells and might be the basis for contraindication in pediatric patients.

Zusammenfassung

Ciprofloxacin ist eine hochwirksame antibakterielle Substanz, die in großem Umfang bei Knochen- und Gelenkinfektionen eingesetzt wird. Berichte über das chondrotoxische Potential dieser Substanz bei Tieren gab Anlaß für Experimente an menschlichen Knorpelzellen in Flüssig- und Agarose-Gel-Kultur. Als Beweis für die proliferationshemmende Wirkung von Ciprofloxacin bei Konzentrationen von 0,5 und 5 mg/l. d.h. Spiegeln, die den therapeutischen beziehungsweise toxischen Serumspiegeln entsprechen, ist die Abnahme der3H-Thymidine-Aufnahme und der Bromdeoxyuridin-Markierung anzusehen. Die durch35SO4-Inkorporation ermittelte Proteoglykan-Synthese ließ keinen Hemmeffekt von Ciprofloxacin erkennen. Immunhistochemisch waren keine Veränderungen in der Morphologie oder den Färbemustern für Prokollagen Typ I, Kollagen Typ II, Keratansulfat und nicht verschwefeltes Chondroitin festzustellen. Da die Hemmung der DNA-Synthese in Abhängigkeit von verschiedenen Ciprofloxacin-Konzentrationen variierte, ist auf einen gezielten Effekt auf neu sich differenzierende Zellen zu schließen. Möglicherweise ist dies die Basis für die Kontraindikation gegen eine therapeutische Anwendung der Substanz bei pädiatrischen Patienten.

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Authors and Affiliations

  1. Orthopaedic Research Laboratory, Dept. of Orthopaedic Surgery, Div. of Arthritis Surgery, The Johns Hopkins Medical Institutions, The Good Samaritan Hospital, 5601 Loch Raven Boulevard, 212339, Baltimore, MD, USA

    M. A. Mont M. D., S. K. Mathur M. D., Carmelita G. Frondoza Ph. D. & D. S. Hungerford M. D.

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  1. M. A. Mont M. D.
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  2. S. K. Mathur M. D.
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  3. Carmelita G. Frondoza Ph. D.
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  4. D. S. Hungerford M. D.
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Mont, M.A., Mathur, S.K., Frondoza, C.G. et al. The effects of ciprofloxacin on human chondrocytes in cell culture. Infection 24, 151–155 (1996). https://doi.org/10.1007/BF01713325

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