Document Detail

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) improves the innate immune response and enhances survival in murine polymicrobial sepsis.
MedLine Citation:
PMID:  20657274     Owner:  NLM     Status:  MEDLINE    
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. DESIGN: Experimental animal model. SETTING: University laboratory. SUBJECTS: C57BL/6 mice. INTERVENTIONS: 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. MEASUREMENTS AND MAIN 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. CONCLUSION: 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.
Katharina Cziupka; Alexandra Busemann; Lars Ivo Partecke; Christian Pötschke; Matthias Rath; Tobias Traeger; Pia Koerner; Wolfram von Bernstorff; Wolfram Kessler; Stephan Diedrich; Frank Ulrich Weiss; Stefan Maier; Barbara M Bröker; Claus-Dieter Heidecke
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Critical care medicine     Volume:  38     ISSN:  1530-0293     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-20     Completed Date:  2010-11-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2169-74     Citation Subset:  AIM; IM    
Department of Surgery, Ernst-Moritz-Arndt University Greifswald, Germany.
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MeSH Terms
Apoptosis / drug effects,  immunology
Chemokines / blood
Cytokines / blood
Disease Models, Animal
Immunity, Innate / drug effects,  immunology
Injections, Intravenous
Mice, Inbred C57BL
Neutrophil Infiltration / immunology
Neutrophils / immunology
Peritoneal Cavity / microbiology
Peritonitis / drug therapy,  immunology,  mortality
Receptors, TNF-Related Apoptosis-Inducing Ligand / biosynthesis
Recombinant Proteins / therapeutic use
Sepsis / drug therapy*,  immunology,  mortality
TNF-Related Apoptosis-Inducing Ligand / therapeutic use*
Reg. No./Substance:
0/Chemokines; 0/Cytokines; 0/Receptors, TNF-Related Apoptosis-Inducing Ligand; 0/Recombinant Proteins; 0/TNF-Related Apoptosis-Inducing Ligand

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