Effects of moxifloxacin in zymogen A or S. aureus stimulated human THP-1 monocytes on the inflammatory process and the spread of infection

Hall, Iris H.; Schwab, Ute; Ward, E. Stacy; Ives, Timothy J.

doi:10.1016/s0024-3205(03)00611-8

Cited by 19 publications

(17 citation statements)

References 27 publications

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“…In human blood, monocytes or THP-1 cells activated with lipopolysaccharide, preincubation with moxifloxacin (5-20 mg/ml) for at least 4 h caused concentrationdependent inhibition of the synthesis of IL-1b, IL-8 and TNF-a, in association with the reduced expression of the transcription factors, nuclear factor kappa B (NFkB), ERK and c-Jun N-terminal kinase [21 ]. A possible explanation for this apparent contradiction (apart from the different cytokines and cell types analysed) may be that the effect of moxifloxacin on THP-1 monocytic cells, stimulated in vitro with zymogen A or S. aureus, has been shown to be temporally biphasic [22]. Within the first hour, moxifloxacin increased the release of nitric oxide and hydrogen peroxide, but after 4 h lipid peroxidation, lysosomal enzyme release and the release of proinflammatory cytokines were inhibited.…”

Section: Effects On Leukocyte Function and Cytokine Expressionmentioning

confidence: 99%

Immunomodulatory effects of antimicrobials in the therapy of respiratory tract infections

Parnham

2005

Current Opinion in Infectious Diseases

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Macrolides can facilitate the killing of microorganisms in acute respiratory infections through the stimulation of neutrophil activation. On long-term administration, anti-inflammatory, T helper type 1 lymphocyte-enhancing and biofilm-thinning actions, among others, make macrolides valid therapeutic options in chronic infectious/inflammatory disorders, even for infections with microorganisms that are not completely eradicated.

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Section: Effects On Leukocyte Function and Cytokine Expressionmentioning

confidence: 99%

Immunomodulatory effects of antimicrobials in the therapy of respiratory tract infections

Parnham

2005

Current Opinion in Infectious Diseases

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“…These effects occur at clinically relevant concentrations and are claimed to explain increased susceptibility to mycobacterial infections and immunomodulatory properties of macrolides in cystic fibrosis patients receiving chronic treatment with the drug (4,5). Conversely, the fluoroquinolone moxifloxacin does not interfere with neutrophil functions (6) but stimulates the oxidative burst in monocytes (7) and modulates immune response (8), which may contribute to the beneficial effects of fluoroquinolones on infection control in clinics (8).…”

mentioning

confidence: 99%

Study of Macrophage Functions in Murine J774 Cells and Human Activated THP-1 Cells Exposed to Oritavancin, a Lipoglycopeptide with High Cellular Accumulation

Lemaire

Mingeot‐Leclercq

Tulkens

et al. 2014

Antimicrob Agents Chemother

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Oritavancin, a lipoglycopeptide antibiotic in development, accumulates to high levels in the lysosomes of eukaryotic cells. We examined specific functions of macrophages (phagocytic capacity, lysosomal integrity, metabolic activity, and production of reactive oxygen species [ROS]) in correlation with the cellular accumulation of the drug, using J774 mouse macrophages and THP-1 human monocytes differentiated into macrophages using phorbol 12-myristate 13-acetate. Oritavancin did not affect Pseudomonas aeruginosa phagocytosis, lysosomal integrity, or metabolic activity in cells incubated for 3 h with extracellular concentrations ranging from 5 to 50 g/ml. At extracellular concentrations of >25 g/ml, oritavancin reduced latex bead phagocytosis by approximately 50% and doubled ROS production in J774 macrophages only. This may result from the fact that the cellular accumulation of oritavancin was 15 times higher in J774 cells than in activated THP-1 cells at 3 h. Human pharmacokinetic studies estimate that the concentration of oritavancin in alveolar macrophages could reach approximately 560 g/ml after administration of a cumulative dose of 4 g, which is below the cellular concentration needed in the present study to impair latex bead phagocytosis (1,180 g/ml) or to stimulate ROS production (15,000 g/ml) by J774 cells. The data, therefore, suggest that, in spite of its substantial cellular accumulation, oritavancin is unlikely to markedly affect macrophage functions under the conditions of use investigated in current phase III trials (a single dose of 1,200 mg).

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“…67 This observation was also in agreement with previous studies describing the suppression of ROS by MOX so that lipid peroxidation and tissue destruction due to the infection process is suppressed. 68 Since, it has been reported that an increase in cytokine levels, i.e., TNF-α and IL-6, 69−72 in-directly leads to an increase in tissue inflammatory conditions. Reduction of levels of inflammatory cytokines (TNF-α and IL-6) in plasma by MONe6 was beneficial in hyperinflammatory conditions associated with cIAIs as both tocopheryl succinate and MOX (via NFκB inhibition) 51,73−75 has been reported to reduce cytokine levels 73,76 via reducing NFκB expression from macrophages and THP1 monocytes.…”

Section: Discussionmentioning

confidence: 99%

Moxifloxacin-Loaded Nanoemulsions Having Tocopheryl Succinate as the Integral Component Improves Pharmacokinetics and Enhances Survival inE. coli-Induced Complicated Intra-Abdominal Infection

Shukla

Verma²,

Dwivedi

et al. 2014

Mol. Pharmaceutics

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In the present work, a novel nanoemulsion laden with moxifloxacin has been developed for effective management of complicated intra-abdominal infections. Moxifloxacin nanoemulsion fabricated using high pressure homogenization was evaluated for various pharmaceutical parameters, pharmacokinetics (PK) and pharmacodynamics (PD) in rats with E. coli-induced peritonitis and sepsis. The developed nanoemulsion MONe6 (size 168 ± 28 nm and zeta potential (ZP) 24.78 ± 0.45 mV, respectively) was effective for intracellular delivery and sustaining the release of MOX. MONe6 demonstrated improved plasma (AUC(MONe6/MOX) = 2.38-fold) and tissue pharmacokinetics of MOX (AUC(MONe6/MOX) = 2.63 and 1.47 times in lung and liver, respectively). Calculated PK/PD index correlated well with a reduction in bacterial burden in plasma as well as tissues. Enhanced survival on treatment with MONe6 (65.44%) and as compared to the control group (8.22%) was a result of reduction in lipid peroxidation, neutrophil migration, and cytokine levels (TNF-α and IL6) as compared to untreated groups in the rat model of E. coli-induced sepsis. Parenteral nanoemulsions of MOX hold a promising advantage in the therapy of E. coli-induced complicated intra-abdominal infections and is helpful in the prevention of further complications like septic shock and death.

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Effects of moxifloxacin in zymogen A or S. aureus stimulated human THP-1 monocytes on the inflammatory process and the spread of infection

Cited by 19 publications

References 27 publications

Immunomodulatory effects of antimicrobials in the therapy of respiratory tract infections

Immunomodulatory effects of antimicrobials in the therapy of respiratory tract infections

Study of Macrophage Functions in Murine J774 Cells and Human Activated THP-1 Cells Exposed to Oritavancin, a Lipoglycopeptide with High Cellular Accumulation

Moxifloxacin-Loaded Nanoemulsions Having Tocopheryl Succinate as the Integral Component Improves Pharmacokinetics and Enhances Survival inE. coli-Induced Complicated Intra-Abdominal Infection

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