title: Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome.
abstract: Rats with Metabolic Syndrome (MetaS) have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S.) aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS) and high capacity runner (HCR) rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF), and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS) rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses.
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California, United States of America; Department of Anesthesiology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Mervyn
authors.initials: M
authors.lastname: Maze
authors.affiliation: Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Koch
authors.affiliation: Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Britton
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Judith
authors.initials: J
authors.lastname: Hellman
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D054426:Chemokine CXCL2 / Q000032:analysis / Q000097:blood; D005260:Female; D016753:Interleukin-10 / Q000032:analysis / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood; D008168:Lung / Q000737:chemistry / Q000276:immunology; D024821:Metabolic Syndrome / Q000150:complications* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000150:complications* / Q000276:immunology
chemical_list: D054426:Chemokine CXCL2; C513296:Cxcl2 protein, rat; D020381:Interleukin-17; D015850:Interleukin-6; D016753:Interleukin-10