title: Thymic stromal lymphopoietin mediates the host response and increases mortality during sepsis.
abstract: BACKGROUND
  Sepsis and subsequent multiorgan system failure is associated with high rates of mortality and morbidity. Thymic stromal lymphopoietin (TSLP) is a cytokine that can be produced by keratinocytes and epithelial cells. Primarily, TSLP has been shown to promote counter-inflammatory processes. However, its potential expression or role in the pathogenesis of sepsis is largely unexplored. We hypothesized that TSLP is expressed during sepsis and TSLP blockade would alter the immune response and mortality.
  
  
  METHODS
  Mice underwent cecal ligation and puncture (CLP) to produce a physiologically relevant murine model for sepsis. Cohorts were either treated with neutralizing TSLP antibodies or isotype controls before the CLP to determine changes in survival, bacterial loads, cytokine levels, and neutrophil function.
  
  
  RESULTS
  It was observed that TSLP levels peaked at 6 h and remained detectable up to 48 h after CLP. Mice pretreated with neutralizing TSLP showed decreased mortality and bacterial load after CLP. Additionally, we determined that septic mice pretreated with the anti-TSLP antibody had increased tumor necrosis factor alpha and oxidative burst as well as increased interleukin 17 and neutrophil numbers compared with mice pretreated with isotype controls.
  
  
  CONCLUSIONS
  TSLP levels peak early but are sustained during the first 48 h of sepsis. We speculate that TSLP blunts the neutrophil response resulting in increased bacterial load and mortality.
authors.affiliation: Division of Research, Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Kuethe
authors.affiliation: Division of Research, Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Priya S
authors.initials: PS
authors.lastname: Prakash
authors.affiliation: Division of Research, Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Emily F
authors.initials: EF
authors.lastname: Midura
authors.affiliation: Division of Research, Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Bobby L
authors.initials: BL
authors.lastname: Johnson
authors.affiliation: Division of Research, Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Kasten
authors.affiliation: Division of Research, Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, Ohio. Electronic address: charles.caldwell@uc.edu.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Caldwell
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016470:Bacteremia / Q000276:immunology / Q000378:metabolism / Q000401:mortality; D002432:Cecum / Q000293:injuries; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D008815:Mice, Inbred Strains; D009102:Multiple Organ Failure / Q000276:immunology / Q000378:metabolism / Q000401:mortality; D009504:Neutrophils / Q000276:immunology; D016897:Respiratory Burst / Q000187:drug effects / Q000276:immunology; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism / Q000401:mortality*; D015996:Survival Rate; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse
keywords: Bacteremia; Cecal ligation and puncture; Cytokines; Neutrophils; Oxidative burst