Immunomodulatory Action of Levofloxacin on Cytokine Production by Human Peripheral Blood Mononuclear Cells

Abstract

Levofloxacin (LVFX), the bacteriologically active isomer of ofloxacin, is a fluorinated quinolone. LVFX suppressed the proliferative activity of peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin (PHA). LVFX increased interleukin-2 (IL-2) production by PBMC stimulated with PHA in a dose-dependent manner, with more than 10 μg/ml of LVFX causing a significant increase. The granulocyte-macrophage colony-stimulating factor and soluble IL-2 receptor production by PHA-stimulated PBMC was suppressed at high concentrations of LVFX. Interleukin-1β production by lipopolysaccharide-stimulated PBMC was suppressed in a concentration-dependent manner by LVFX, and tumor necrosis factor-α production was suppressed at only the highest concentration. In contrast, interleukin-8 production was little affected by LVFX. These results show that LVFX has an immunomodulatory action on cytokines production by PBMC independent of its antimicrobial activity.

Levofloxacin Inhibits Rhinovirus Infection in Primary Cultures of Human Tracheal Epithelial Cells

“…In the present study, LVFX reduced the RV14 infection-induced production of IL-1␤, IL-6, and IL-8. The inhibitory effects of LVFX on IL-1␤ production are consistent with previous findings for LPS-stimulated peripheral blood mononuclear cells (46), although IL-8 production was affected little by LVFX. Trovafloxacin reduces the production of IL-6 and IL-1␤ by human monocytes in response to LPS stimulation (13).…”

Ciprofloxacin enhances the stimulation of matrix metalloproteinase 3 expression by interleukin‐1β in human tendon‐derived cells

“…First, fluoroquinolones have been shown to induce localized inflammation of the paratenon surrounding rat Achilles tendon (3). Second, fluoroquinolones have been shown to enhance the expression of certain interleukins and other cytokines (5,6). Our results raise the possibility that a combination of fluoroquinolone and (fluoroquinolone-induced) inflammatory mediators might result in the inappropriate or unbalanced expression of MMPs.…”

“…Inflammation of the paratenon and degenerative changes in tendon cells have been noted in studies of fluoroquinolone-treated animals (3,4). Fluoroquinolones have been shown to have a number of effects on various mammalian cell types in culture, including both increased and decreased expression of inflammatory mediators (5,6), reduced expression of some extracellular matrix proteins (7,8), reduced mitochondrial activity (8), and noncytotoxic inhibition of canine tendon cell proliferation (7).…”

Anti-Inflammatory Effects of Moxifloxacin on Activated Human Monocytic Cells: Inhibition of NF-κB and Mitogen-Activated Protein Kinase Activation and of Synthesis of Proinflammatory Cytokines

“…The findings from previous in vivo studies (35) and the present in vitro data, which demonstrate and expand our understanding of the anti-inflammatory effects of MXF, provide further support for other observations relating to modulation of the inflammatory response by other quinolone compounds. In vitro studies with LPS-stimulated human monocytes have shown that ciprofloxacin, trovafloxacin, moxifloxacin, grepafloxacin, and levofloxacin have inhibitory effects on various proinflammatory cytokines, mainly IL-1␣, IL-1␤, ⌻⌵F-␣, IL-6, and IL-8 (3,5,9,21,30,45,47). Reduction of IL-8 levels was also found in stimulated human airway cells after treatment with grepafloxacin (15).…”