Pleiotropic effects of levofloxacin, fluoroquinolone antibiotics, against influenza virus-induced lung injury

© 2015 Enoki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Reactive oxygen species (ROS) and nitric oxide (NO) are major pathogenic molecules produced during viral lung infections, including influenza. While fluoroquinolones are widely used as antimicrobial agents for treating a variety of bacterial infections, including secondary infections associated with the influenza virus, it has been reported that they also function as anti-oxidants against ROS and as a NO regulator. Therefore, we hypothesized that levofloxacin (LVFX), one of the most frequently used fluoroquinolone derivatives, may attenuate pulmonary injuries associated with influenza virus infections by inhibiting the production of ROS species such as hydroxyl radicals and neutrophil-derived NO that is produced during an influenza viral infection. The therapeutic impact of LVFX was examined in a PR8 (H1N1) influenza virus-induced lung injury mouse model. ESR spin-trapping experiments indicated that LVFX showed scavenging activity against neutrophil-derived hydroxyl radicals. LVFX markedly improved the survival rate of mice that were infected with the influenza virus in a dose-dependent manner. In addition, the LVFX treatment resulted in a dose-dependent decrease in the level of 8-hydroxy-2'-deoxyguanosine (a marker of oxidative stress) and nitrotyrosine (a nitrative marker) in the lungs of virus-infected mice, and the nitrite/nitrate ratio (NO metabolites) and IFN-? in BALF. These results indicate that LVFX may be of substantial benefit in the treatment of various acute inflammatory disorders such as influenza virus-induced pneumonia, by inhibiting inflammatory cell responses and suppressing the overproduction of NO in the lungs

Influence of subinhibitory concentrations of protein-synthesis-inhibiting antibiotics on production and release of the pneumococcal virulence factor pneumolysin in vitro

Objective: Pneumolysin is an important virulence factor of Streptococcus pneumoniae with cytotoxic and proinflammatory activities released during growth and autolysis. At concentrations above the minimal inhibitory concentration, the protein-synthesis-inhibiting antibiotics erythromycin, clindamycin and rifampicin inhibit the production and/or release of virulence factors in various bacterial species. We investigated the influence of subinhibitory concentrations of these antibiotics on production and release of pneumolysin by S. pneumoniae strain D39. Methods: The pneumococcal strain D39 was grown in broth and treated with antibiotics at a concentration of 1/32 of the respective minimal inhibitory concentration. Cytoplasmic and extracellular pneumolysin was measured by quantitative immunoblotting with recombinant pneumolysin as standard. Results: The subinhibitory antibiotic concentrations evaluated did not affect bacterial growth. During logarithmic growth, production of pneumolysin was decreased by clindamycin, erythromycin and rifampicin by approximately 50% compared with untreated controls. The release of pneumolysin was decreased to a similar extent. Conclusion: A decrease in pneumolysin production by 50% probably has a moderate biological effect. We do not advocate the use of subinhibitory concentrations of antibiotics to modulate the expression of virulence factors during pneumococcal disease, particularly with regard to the risk of development of antibiotic resistance. Copyright (C) 2007 S. Karger AG, Basel