title: Linezolid Exerts Greater Bacterial Clearance but No Modification of Host Lung Gene Expression Profiling: A Mouse MRSA Pneumonia Model.
abstract: Linezolid (LZD) is beneficial to patients with MRSA pneumonia, but whether and how LZD influences global host lung immune responses at the mRNA level during MRSA-mediated pneumonia is still unknown.
  
  
  
  A lethal mouse model of MRSA pneumonia mediated by USA300 was employed to study the influence of LZD on survival, while the sublethal mouse model was used to examine the effect of LZD on bacterial clearance and lung gene expression during MRSA pneumonia. LZD (100mg/kg/day, IP) was given to C57Bl6 mice for three days. On Day 1 and Day 3 post infection, bronchoalveolar lavage fluid (BALF) protein concentration and levels of cytokines including IL6, TNFα, IL1β, Interferon-γ and IL17 were measured. In the sublethal model, left lungs were used to determine bacterial clearance and right lungs for whole-genome transcriptional profiling of lung immune responses.
  
  
  
  LZD therapy significantly improved survival and bacterial clearance. It also significantly decreased BALF protein concentration and levels of cytokines including IL6, IL1β, Interferon-γ and IL17. No significant gene expression changes in the mouse lungs were associated with LZD therapy.
  
  
  
  LZD is beneficial to MRSA pneumonia, but it does not modulate host lung immune responses at the transcriptional level.
authors.affiliation: Department of Medicine, Northwestern University, Chicago, Illinois, United States of America ; Section of Pulmonary, Critical Care Medicine, Allergy and Sleep, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Jiwang
authors.initials: J
authors.lastname: Chen
authors.forename: Gang
authors.initials: G
authors.lastname: Feng
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.forename: Juliane B
authors.initials: JB
authors.lastname: Wardenburg
authors.forename: Simon
authors.initials: S
authors.lastname: Lin
authors.forename: Ichiro
authors.initials: I
authors.lastname: Inoshima
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
authors.forename: Richard G
authors.initials: RG
authors.lastname: Wunderink
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D000069349:Linezolid / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008809:Mice, Inbred C3H; D046228:Microarray Analysis; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D016207:Cytokines; D000069349:Linezolid