Linezolid decreases susceptibility to secondary bacterial pneumonia postinfluenza infection in mice through its effects on IFN-γ.

Academic Article


  • Influenza infection predisposes patients to secondary bacterial pneumonia that contributes significantly to morbidity and mortality. Although this association is well documented, the mechanisms that govern this synergism are poorly understood. A window of hyporesponsiveness following influenza infection has been associated with a substantial increase in local and systemic IFN-γ concentrations. Recent data suggest that the oxazolidinone antibiotic linezolid decreases IFN-γ and TNF-α production in vitro from stimulated PBMCs. We therefore sought to determine whether linezolid would reverse immune hyporesponsiveness after influenza infection in mice through its effects on IFN-γ. In vivo dose-response studies demonstrated that oral linezolid administration sufficiently decreased bronchoalveolar lavage fluid levels of IFN-γ at day 7 postinfluenza infection in a dose-dependent manner. The drug also decreased morbidity as measured by weight loss compared with vehicle-treated controls. When mice were challenged intranasally with Streptococcus pneumoniae 7 d postinfection with influenza, linezolid pretreatment led to decreased IFN-γ and TNF-α production, decreased weight loss, and lower bacterial burdens at 24 h postbacterial infection in comparison with vehicle-treated controls. To determine whether these effects were due to suppression of IFN-γ, linezolid-treated animals were given intranasal instillations of rIFN-γ before challenge with S. pneumoniae. This partially reversed the protective effects observed in the linezolid-treated mice, suggesting that the modulatory effects of linezolid are mediated partially by its ability to blunt IFN-γ production. These results suggest that IFN-γ, and potentially TNF-α, may be useful drug targets for prophylaxis against secondary bacterial pneumonia following influenza infection.
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    Published In


  • Acetamides, Animals, Anti-Bacterial Agents, Bacterial Load, Bronchoalveolar Lavage Fluid, CD4 Lymphocyte Count, Coinfection, Disease Susceptibility, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Female, Influenza A virus, Interferon-gamma, Linezolid, Lung, Mice, Mice, Inbred C57BL, Orthomyxoviridae Infections, Oxazolidinones, Pneumonia, Pneumococcal, Recombinant Proteins, Tumor Necrosis Factor-alpha, Viral Load, Virus Replication
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    Author List

  • Breslow-Deckman JM; Mattingly CM; Birket SE; Hoskins SN; Ho TN; Garvy BA; Feola DJ
  • Start Page

  • 1792
  • End Page

  • 1799
  • Volume

  • 191
  • Issue

  • 4