Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) improves the innate immune response and enhances survival in murine polymicrobial sepsis.
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.
Cziupka
Katharina
K
Department of Surgery, Ernst-Moritz-Arndt University Greifswald, Germany. cziupka@uni-greifswald.de
Busemann
Alexandra
A
Partecke
Lars Ivo
LI
Pötschke
Christian
C
Rath
Matthias
M
Traeger
Tobias
T
Koerner
Pia
P
von Bernstorff
Wolfram
W
Kessler
Wolfram
W
Diedrich
Stephan
S
Weiss
Frank Ulrich
FU
Maier
Stefan
S
Bröker
Barbara M
BM
Heidecke
Claus-Dieter
CD
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*
D018925:Chemokines; D016207:Cytokines; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand