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Antimicrobial Agents and Chemotherapy, July 1998, p. 1713-1717, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Effect of Trovafloxacin on Production of Cytokines by Human Monocytes

Anis A. Khan,1,2 Teri R. Slifer,1 and Jack S. Remington1,2,*

Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, Palo Alto, California 94301,1 and Division of Infectious Disease and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California 943052

Received 18 December 1997/Returned for modification 3 February 1998/Accepted 6 May 1998

Antibiotics have previously been shown to have immunomodulatory effects. We examined the effect of the broad-spectrum fluoroquinoline antibiotic trovafloxacin on cytokine synthesis by monocytes obtained from healthy human volunteers and stimulated with either lipopolysaccharide or gram-positive cells (heat-killed Staphylococcus aureus [Pansorbin]). Trovafloxacin levels achievable in humans suppressed in vitro synthesis of each of the cytokines analyzed, viz., interleukin-1alpha (IL-1alpha ), IL-1beta , IL-6, IL-10, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha. This effect was not due to direct effects of the drug on cellular viability; at these concentrations, trovafloxacin did not have demonstrable cytotoxicity for the monocytes, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Although similar patterns of suppression of cytokine synthesis were observed in samples obtained from the same volunteers on different days, there were significant day-to-day variations. These results reveal that trovafloxacin possesses significant immunomodulatory activity in vitro and suggest that suppression of acute-phase inflammatory responses may occur in vivo, elicited through trovafloxacin's effect on cytokine synthesis by human monocytes.

* Corresponding author. Mailing address: Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, 860 Bryant St., Palo Alto, CA 94301. Phone: (650) 853-6061. Fax: (650) 329-9853.

Antimicrobial Agents and Chemotherapy, July 1998, p. 1713-1717, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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