title: Effect of trovafloxacin on production of cytokines by human monocytes.
abstract: 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-1 alpha (IL-1 alpha), IL-1 beta, 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.
authors.affiliation: Department of Immunology and Infectious Diseases, Palo Alto Medical Foundation, California 94301, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Khan
authors.forename: T R
authors.initials: TR
authors.lastname: Slifer
authors.forename: J S
authors.initials: JS
authors.lastname: Remington
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D024841:Fluoroquinolones; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009287:Naphthyridines / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D016207:Cytokines; D024841:Fluoroquinolones; D009287:Naphthyridines; C080163:trovafloxacin