Linezolid has unique immunomodulatory effects in post-influenza community acquired MRSA pneumonia.
INTRODUCTION:Post influenza pneumonia is a leading cause of mortality and morbidity, with mortality rates approaching 60% when bacterial infections are secondary to multi-drug resistant (MDR) pathogens. Staphylococcus aureus, in particular community acquired MRSA (cMRSA), has emerged as a leading ca...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4312022?pdf=render |
| _version_ | 1818910759752564736 |
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| author | Urvashi Bhan Amy B Podsiad Melissa A Kovach Megan N Ballinger Venkateshwar Keshamouni Theodore J Standiford |
| author_facet | Urvashi Bhan Amy B Podsiad Melissa A Kovach Megan N Ballinger Venkateshwar Keshamouni Theodore J Standiford |
| author_sort | Urvashi Bhan |
| collection | DOAJ |
| description | INTRODUCTION:Post influenza pneumonia is a leading cause of mortality and morbidity, with mortality rates approaching 60% when bacterial infections are secondary to multi-drug resistant (MDR) pathogens. Staphylococcus aureus, in particular community acquired MRSA (cMRSA), has emerged as a leading cause of post influenza pneumonia. HYPOTHESIS:Linezolid (LZD) prevents acute lung injury in murine model of post influenza bacterial pneumonia. METHODS:Mice were infected with HINI strain of influenza and then challenged with cMRSA at day 7, treated with antibiotics (LZD or Vanco) or vehicle 6 hours post bacterial challenge and lungs and bronchoalveolar lavage fluid (BAL) harvested at 24 hours for bacterial clearance, inflammatory cell influx, cytokine/chemokine analysis and assessment of lung injury. RESULTS:Mice treated with LZD or Vanco had lower bacterial burden in the lung and no systemic dissemination, as compared to the control (no antibiotic) group at 24 hours post bacterial challenge. As compared to animals receiving Vanco, LZD group had significantly lower numbers of neutrophils in the BAL (9×10(3) vs. 2.3×10(4), p < 0.01), which was associated with reduced levels of chemotactic chemokines and inflammatory cytokines KC, MIP-2, IFN-γ, TNF-α and IL-1β in the BAL. Interestingly, LZD treatment also protected mice from lung injury, as assessed by albumin concentration in the BAL post treatment with H1N1 and cMRSA when compared to vanco treatment. Moreover, treatment with LZD was associated with significantly lower levels of PVL toxin in lungs. CONCLUSION:Linezolid has unique immunomodulatory effects on host inflammatory response and lung injury in a murine model of post-viral cMRSA pneumonia. |
| first_indexed | 2024-12-19T22:47:55Z |
| format | Article |
| id | doaj.art-162970e7e382402fa2d7011be722a3dc |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T22:47:55Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-162970e7e382402fa2d7011be722a3dc2022-12-21T20:02:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01101e011457410.1371/journal.pone.0114574Linezolid has unique immunomodulatory effects in post-influenza community acquired MRSA pneumonia.Urvashi BhanAmy B PodsiadMelissa A KovachMegan N BallingerVenkateshwar KeshamouniTheodore J StandifordINTRODUCTION:Post influenza pneumonia is a leading cause of mortality and morbidity, with mortality rates approaching 60% when bacterial infections are secondary to multi-drug resistant (MDR) pathogens. Staphylococcus aureus, in particular community acquired MRSA (cMRSA), has emerged as a leading cause of post influenza pneumonia. HYPOTHESIS:Linezolid (LZD) prevents acute lung injury in murine model of post influenza bacterial pneumonia. METHODS:Mice were infected with HINI strain of influenza and then challenged with cMRSA at day 7, treated with antibiotics (LZD or Vanco) or vehicle 6 hours post bacterial challenge and lungs and bronchoalveolar lavage fluid (BAL) harvested at 24 hours for bacterial clearance, inflammatory cell influx, cytokine/chemokine analysis and assessment of lung injury. RESULTS:Mice treated with LZD or Vanco had lower bacterial burden in the lung and no systemic dissemination, as compared to the control (no antibiotic) group at 24 hours post bacterial challenge. As compared to animals receiving Vanco, LZD group had significantly lower numbers of neutrophils in the BAL (9×10(3) vs. 2.3×10(4), p < 0.01), which was associated with reduced levels of chemotactic chemokines and inflammatory cytokines KC, MIP-2, IFN-γ, TNF-α and IL-1β in the BAL. Interestingly, LZD treatment also protected mice from lung injury, as assessed by albumin concentration in the BAL post treatment with H1N1 and cMRSA when compared to vanco treatment. Moreover, treatment with LZD was associated with significantly lower levels of PVL toxin in lungs. CONCLUSION:Linezolid has unique immunomodulatory effects on host inflammatory response and lung injury in a murine model of post-viral cMRSA pneumonia.http://europepmc.org/articles/PMC4312022?pdf=render |
| spellingShingle | Urvashi Bhan Amy B Podsiad Melissa A Kovach Megan N Ballinger Venkateshwar Keshamouni Theodore J Standiford Linezolid has unique immunomodulatory effects in post-influenza community acquired MRSA pneumonia. PLoS ONE |
| title | Linezolid has unique immunomodulatory effects in post-influenza community acquired MRSA pneumonia. |
| title_full | Linezolid has unique immunomodulatory effects in post-influenza community acquired MRSA pneumonia. |
| title_fullStr | Linezolid has unique immunomodulatory effects in post-influenza community acquired MRSA pneumonia. |
| title_full_unstemmed | Linezolid has unique immunomodulatory effects in post-influenza community acquired MRSA pneumonia. |
| title_short | Linezolid has unique immunomodulatory effects in post-influenza community acquired MRSA pneumonia. |
| title_sort | linezolid has unique immunomodulatory effects in post influenza community acquired mrsa pneumonia |
| url | http://europepmc.org/articles/PMC4312022?pdf=render |
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