Moxifloxacin modulates inflammation during murine pneumonia.

Christoph Beisswenger,Robert Bals,Anja Honecker,Markus Bischoff,Thomas Tschernig,Andreas Kamyschnikow

doi:10.1186/1465-9921-15-82

Abstract

BackgroundMoxifloxacin is a synthetic antibacterial agent belonging to the fluoroquinolone family. The antimicrobial activity of quinolones against Gram-positive and Gram-negative bacteria is based on their ability to inhibit topoisomerases. Quinolones are described to have immunomodulatory features in addition to their antimicrobial activities. It was the goal of this study to examine whether a short term treatment with moxifloxacin modulates the inflammation during a subsequently induced bacterial infection in an animal model.MethodsMice were treated with moxifloxacin or saline for two consecutive days and were subsequently intranasally infected with viable or heat-inactivated bacterial pathogens (Streptococcus pneumoniae, Pseudomonas aeruginosa) for 6 and 24 hours. Measurements of cytokines in the lungs and plasma were performed. Alveolar cells were determined in bronchoalveolar lavage fluits.ResultsThe inflammation was increased after the inoculation of viable bacteria compared to inactivated bacteria. Numbers of total immune cells and neutrophils and concentrations of inflammatory mediators (e.g. KC, IL-1β, IL-17A) were significantly reduced in lungs of moxifloxacin-treated mice infected with inactivated and viable bacterial pathogens as compared to infected control mice. Plasma concentrations of inflammatory mediators were significantly reduced in moxifloxacin-treated mice. Immunohistochemistry showed a stronger infiltrate of TNF-α-expressing cells into lungs of saline-treated mice infected with viable P. aeruginosa as compared to moxifloxacin-treated mice.ConclusionsThese data show that in this pneumonia model moxifloxacin has anti-inflammatory properties beyond its antibacterial activity.

Highlights

Respiratory tract diseases, such as pneumonia, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD), are worldwide a leading cause of mortality [1]
In vitro studies showed that clinically relevant concentrations of moxifloxacin inhibit the synthesis of inflammatory mediators (e.g. IL-1, TNF-α, IL-6, IL-8) in human peripheral blood mononuclear cells and in the monocytic cell line THP-1 stimulated with LPS, LTA, heat-inactivated bacteria, and Aspergillus fumigatus
Moxifloxacin treatment affects the influx of immune cells into lungs during bacterial pneumonia Moxifloxacin treatment resulted in an increased clearance of P. aeruginosa and S. pneumoniae in the lungs of mice infected with viable bacteria indicating a bactericidal activity of moxifloxacin in our pneumonia model against both bacterial species

Summary

Introduction

Respiratory tract diseases, such as pneumonia, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD), are worldwide a leading cause of mortality [1]. In vitro studies showed that clinically relevant concentrations of moxifloxacin inhibit the synthesis of inflammatory mediators (e.g. IL-1, TNF-α, IL-6, IL-8) in human peripheral blood mononuclear cells and in the monocytic cell line THP-1 stimulated with LPS, LTA, heat-inactivated bacteria, and Aspergillus fumigatus. In vitro studies further revealed that moxifloxacin inhibits the activation of MAP kinase and NF-kB signaling cascades, the synthesis of nitric oxide, and the expression of the chemokines IL-6 and IL-8 in human respiratory epithelial cell lines stimulated with inflammatory cytokines [17,18] To date, it is not sufficiently understood how fluoroquinolones modulate inflammation and the activation of cellular signaling molecules such as NF-κB- or MAP kinases. It was the goal of this study to examine whether a short term treatment with moxifloxacin modulates the inflammation during a subsequently induced bacterial infection in an animal model

Methods

Results

Conclusion