240

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Effect of qidnolones on human neutrophil cberoo taxis J Antimicrob Chemother 1992: 30: 240-242 Sir, Neutrophils play an important role in host defence against infections (Wright, 1982). Although quinolones are frequently administered to compromised patients, little is known about the influence of these drugs on neutrophil functions. In this study we investigated the effect of ciprofloxacin, norfloxacin, ofloxacin.

and its optically active isomer S(-)-ofloxacin (levofloxacin) on human neutrophil chemotaxis. Ciprofloxacin (Bayer Co., Ltd), norfloxacin (Kyorin Seiyaku Co., Ltd), ofloxacin (Daiichi Seiyaku Co., Ltd), and levofloxacin (Daiichi Seiyaku Co., Ltd) were dissolved in 0-1 N NaOH and further diluted in phosphatebuffered saline (PBS, pH 7-4) at concentrations of 10-1000 mg/L. Human neutrophils were isolated from the heparinized venous blood of healthy donors by dextran sedimentation and Lymphoprep density gradient centrifugation (Boyum, 1976). Chemotaxis was assessed by Boyden-chamber method (Ishibashi & Yamashita, 1982) using 20% zymosan-activated serum (ZAS), I 0"'M formyl-methionyl-leucylphenylalanine (FMLP), and 10"'M leukotriene B^LTB^ as chemoattractants. Migration distances (/on) of neutrophils were measured after I h incubation by the leading-front method. Norfloxacin ofloxacin, and levofloxacin did not affect neutrophil chemotaxis in concentrations up to 100 mg/L (Table I). On the other hand, the therapeutic concentration (1 mg/L) of ciprofloxacin significantly reduced (26-5%; P < 0-05) neutrophil chemotaxis toward ZAS but not to FMLP or LTB«. The trypan-blue dye exclusion test (Welch. Davis & Thrupp, 1981) revealed that the viability of neutrophils treated with I, 10 and 100 mg/L of ciprofloxacin were > 95%, 75%, and < 5%, respectively. When ciprofloxacin was removed by washing after pre-incubation at 37°C for 30 min with neutrophils or by dialysis after incubation with ZAS, no significant inhibitions were observed in either case (Table II). Therefore, the remarkable inhibition of chemotaxis observed at high concentrations ( > 10 mg/L) of ciprofloxacin might be due to the cytotoxicity for neutrophils. The evaluation of a possible effect of antibiotics on host defences may provide important information for their clinical use in immunocompromised patients. In this report we have shown that ciprofloxacin inhibited neutrophil chemotaxis toward ZAS at a clinically relevant concentration (1 mg/L). This inhibition might be specific for ZAS-induced chemotaxis since ciprofloxacin did not influence FMLP- or LTB4-induced neutrophil chemotaxis. Although the opposite finding has been reported previously (Boogaerts et al., 1986), this discrepancy may be due to the differences in the assay conditions. In our system, chemotaxis was evaluated with drugs and neutrophils both present simultaneously

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Helicobacter pylori. Journal of Clinical Microbiology 29, 51-3. Geis. G., Leying, H., Sucrbaum, S. & Opferkuch, W. (1990). Unusual fatty acid substitution in lipidj and lipopolytaccharides of Helicobacter pylori. Journal of Clinical Microbiology 28, 930-2. Goodwin, C. S., Blake. P. & Blincow, E. (1986). The minimum inhibitory and bactericidal concentrations of antibiotics and anti-ulcer agents against Campylobocter pyloridis. Journal of Antimicrobial Chemotherapy 17, 309-14. Hceres, J., Backx, L. J. J.. Mostmans, J. H. & van Cutsem, J. (1979). Antimycotic imidazoles. Part 4. Synthesis and antifungal activity of ketoconazole, a new potent orally active broad-spectrum antifungal agent. Journal of Medicinal Chemistry 22, 1003-5. Kucers, A. & Bennett, N. McK. (1987). Ketoconazole. In The Use of Antibiotics, 4th edn, pp. 1506-27. Heinemann, London. McNulty, C. A. & Dent, J. C. (1988). Susceptibility of clinical isolates of Campylobacter pylori to twenty-one antimicrobial agents. European Journal of Clinical Microbiology and Infectious Diseases 7, 566-9. Peterson, W. L. (1991). Helicobacter pylori and peptic ulcer disease. New England Journal of Medicine 324, 1043-8. Shadomy, S., Espinel-IngrofT, A. & Cartwright, R. Y. (1985). Laboratory studies with antifungal agents: susceptibility tests and bioassayt. In Manual of Clinical Microbiology, 4th edn (Lennette, E. H., Balows, A., Hausler, W. J. & Shadomy, H. J., Eds), pp. 991-9. American Society for Microbiology, Washington, DC. Skirrow, M. B. (1990). Campylobacter and helicobacter infections of man and animals. In Topley A Wilson's Principles of Bacteriology, Virology and Immunity, 8th ed, Vol. 3: Bacterial Diseases (Smith, G. R. & Easmon, C. S. F., Eds), pp. 531-45. Edward Arnold, London. Washington, J. A. (1985). Susceptibility tests: agar dilution. In Manual of Clinical Microbiology, 4th edn (Lennette. E. H., Balows, A., Hausler, W. J. & Shadomy, H. J., Eds), pp. 967-71. American Society for Microbiology, Washington, DC.

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241

Table 1. Effect of quinolones on neutrophil chemotaxis

Drug Control

0 1 10 100

ZAS

Attractant FMLP

LTB4

53-1317-88

45-8015-22

33-5315-71

39-131810' 32-6711058* 0*

43-8714-21 29-8014-61' 0*

33-2711-27 23-8714-25

43-1313-51 43-7312-82 35-3312-49

31-9311-97 310711-48 33-1311-31



51-5315-61 49-2015-95 49-4016-18

Ofloxadn

1 10 100

51-0715-31 49-8716-72 47-6714-16

45-4014-9! 44-4715-62 38-7312-14

31-3311-50 31-6010-80 27131310

Levofloxacin

1 10 100

52-3316-66 51-2016-89 42-6714-82

44-4013-50 42-7315-14 34-0012-32

31-8712-74 32-4710-53 32-1311-73

Norfloxacin

ZAS, 20% zymosan-activated serum; FMLP, 10"7 M forrnyl-methionylleucyl phenylananine; LTB4, 10"' M leukotriene B4. The values represent the mean ± s-E. of five experiments. 'P

Effect of quinolones on human neutrophil chemotaxis.

240 Correspondence Effect of qidnolones on human neutrophil cberoo taxis J Antimicrob Chemother 1992: 30: 240-242 Sir, Neutrophils play an important...
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