Linezolid dampens neutrophil-mediated inflammation in methicillin-resistant Staphylococcus aureus-induced pneumonia and protects the lung of associated damages.

BACKGROUND Linezolid is considered as a therapeutic alternative to the use of glycopeptides for the treatment of pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). Clinical studies reported a potent survival advantage conferred by the oxazolidinone and called into question the use of glycopeptides as first-line therapy. METHODS In a mouse model of MRSA-induced pneumonia, quantitative bacteriology, proinflammatory cytokine concentrations in lung, myeloperoxidase activity, Ly6G immunohistochemistry, and endothelial permeability were assessed to compare therapeutic efficacy and immunomodulative properties of linezolid and vancomycin administered subcutaneously every 12 hours. RESULTS Significant antibacterial activity was achieved after 48 hours of treatment for linezolid and vancomycin. Levels of interleukin 1β, a major proinflammatory cytokine, and macrophage inflammatory protein 2, a chemokine involved in the recruitment of neutrophils, were decreased by both antimicrobials. Only linezolid was able to dramatically reduce the production of tumor necrosis factor α. Analysis of myeloperoxidase activity and Ly6G immunostaining showed a dramatic decrease of neutrophil infiltration in infected lung tissues for linezolid-treated animals. A time-dependent increase of endothelial permeability was observed for the control and vancomycin regimens. Of interest, in the linezolid group, decreased endothelial permeability was detected 48 hours after infection. CONCLUSIONS Our results indicate that linezolid could be superior to vancomycin for the management of MRSA pneumonia by attenuating an excessive inflammatory reaction and protecting the lung from pathogen-associated damages.