title: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) improves the innate immune response and enhances survival in murine polymicrobial sepsis.
abstract: OBJECTIVE
  To investigate the role of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in postoperative polymicrobial abdominal sepsis.Sepsis is the leading cause of death among critically ill surgical patients. TRAIL is commonly known as an apoptosis-inducing agent in cancer cells. It also plays an important role in the regulation of inflammatory reactions. The role of TRAIL in polymicrobial sepsis is still unclear.
  
  
  METHODS
  Experimental animal model.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  C57BL/6 mice.
  
  
  METHODS
  Colon ascendens stent peritonitis (CASP) was induced in female mice. One hour, 24 hrs, and 48 hrs after induction of CASP, murine recombinant TRAIL was given intravenously.
  
  
  RESULTS
  This study demonstrates a protective effect of TRAIL in CASP, an experimental model of murine polymicrobial sepsis. Intravenous administration of recombinant TRAIL to mice after CASP induction led to highly significantly prolonged survival. The migration of effector cells into the peritoneal cavity was strongly enhanced. Consequently, TRAIL-treated mice eliminated bacteria significantly better from the peritoneal cavity, the source of infection. Systemic spread of gut bacteria was also reduced by several orders of magnitude. As a result of the reduced systemic spread of bacteria, the accumulation of neutrophils within the spleen and mesenteric lymph nodes was strongly decreased.
  
  
  CONCLUSIONS
  TRAIL-treated mice are highly protected from abdominal sepsis. Because diagnosis and therapy are frequently delayed in human sepsis, it is remarkable that TRAIL is effective when given via a therapeutic approach. Therefore, this study suggests a therapeutic potential for TRAIL in human sepsis. This should be addressed in future trials.
authors.affiliation: Department of Surgery, Ernst-Moritz-Arndt University Greifswald, Germany. cziupka@uni-greifswald.de
authors.forename: Katharina
authors.initials: K
authors.lastname: Cziupka
authors.forename: Alexandra
authors.initials: A
authors.lastname: Busemann
authors.forename: Lars Ivo
authors.initials: LI
authors.lastname: Partecke
authors.forename: Christian
authors.initials: C
authors.lastname: Pötschke
authors.forename: Matthias
authors.initials: M
authors.lastname: Rath
authors.forename: Tobias
authors.initials: T
authors.lastname: Traeger
authors.forename: Pia
authors.initials: P
authors.lastname: Koerner
authors.forename: Wolfram
authors.initials: W
authors.lastname: von Bernstorff
authors.forename: Wolfram
authors.initials: W
authors.lastname: Kessler
authors.forename: Stephan
authors.initials: S
authors.lastname: Diedrich
authors.forename: Frank Ulrich
authors.initials: FU
authors.lastname: Weiss
authors.forename: Stefan
authors.initials: S
authors.lastname: Maier
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Bröker
authors.forename: Claus-Dieter
authors.initials: CD
authors.lastname: Heidecke
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D007275:Injections, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010529:Peritoneal Cavity / Q000382:microbiology; D010538:Peritonitis / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000627:therapeutic use*
chemical_list: D018925:Chemokines; D016207:Cytokines; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand