{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:52:07Z","timestamp":1789660327111,"version":"4.0.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T00:00:00Z","timestamp":1375315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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-\u03b3 concentrations. Recent data suggest that the oxazolidinone antibiotic linezolid decreases IFN-\u03b3 and TNF-\u03b1 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-\u03b3. In vivo dose-response studies demonstrated that oral linezolid administration sufficiently decreased bronchoalveolar lavage fluid levels of IFN-\u03b3 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-\u03b3 and TNF-\u03b1 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-\u03b3, linezolid-treated animals were given intranasal instillations of rIFN-\u03b3 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-\u03b3 production. These results suggest that IFN-\u03b3, and potentially TNF-\u03b1, may be useful drug targets for prophylaxis against secondary bacterial pneumonia following influenza infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1300180","type":"journal-article","created":{"date-parts":[[2013,7,6]],"date-time":"2013-07-06T00:47:58Z","timestamp":1373071678000},"page":"1792-1799","source":"Crossref","is-referenced-by-count":20,"title":["Linezolid Decreases Susceptibility to Secondary Bacterial Pneumonia Postinfluenza Infection in Mice Through its Effects on IFN-\u03b3"],"prefix":"10.1093","volume":"191","author":[{"given":"Jessica M","family":"Breslow-Deckman","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine , Lexington, KY 40536"},{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Kentucky College of Medicine , Lexington, KY 40536"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia M","family":"Mattingly","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy , Lexington, KY 40536"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E","family":"Birket","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy , Lexington, KY 40536"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha N","family":"Hoskins","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine , Lexington, KY 40536"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam N","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy , Lexington, KY 40536"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth A","family":"Garvy","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine , Lexington, KY 40536"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Feola","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy , Lexington, KY 40536"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,8,15]]},"reference":[{"key":"2025032405195194200_r1","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1086\/591708","article-title":"Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness","volume":"198","author":"Morens","year":"2008","journal-title":"J. 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