Toll-like receptor 4 deficiency and acute pancreatitis act similarly in reducing host defense during murine Escherichia coli peritonitis.
Crit Care Med
; 33(5): 1036-43, 2005 May.
Article
in En
| MEDLINE
| ID: mdl-15891333
ABSTRACT
OBJECTIVE:
Acute pancreatitis is frequently complicated by Gram-negative sepsis. Mammalian cells recognize lipopolysaccharide from Gram-negative bacteria via Toll-like receptor (TLR) 4. The objective of this study was to determine the role of TLR4 in the defense against Gram-negative sepsis in previously healthy mice and in animals with preexisting pancreatitis.DESIGN:
A controlled, in vivo laboratory study.SETTING:
Research laboratory of a health sciences university.SUBJECTS:
Female C3H/HeJ (nonfunctional TLR4 mutant) and C3H/HeN (wild-type) mice.INTERVENTIONS:
Abdominal sepsis was induced by the intraperitoneal injection of Escherichia coli. Pancreatitis was induced by 12 hourly intraperitoneal injections of cerulein. MEASUREMENTS AND MAINRESULTS:
The following experiments were performed. First, healthy TLR4 mutant mice demonstrated an enhanced bacterial load and dissemination of the infection relative to wild-type mice after intraperitoneal injection with E. coli, associated with a reduced early release of proinflammatory cytokines and an attenuated influx of neutrophils into the peritoneal fluid. Second, wild-type mice in which acute pancreatitis was induced by repeated cerulein injections showed an increased bacterial load and dissemination of E. coli relative to wild-type mice without pancreatitis, which was accompanied by a blunted proinflammatory cytokine response by peritoneal macrophages ex vivo and a diminished early cytokine and neutrophil response in vivo. Third, whereas the severity of cerulein-induced pancreatitis was similar in TLR4 mutant and wild-type mice, the important contribution of TLR4 to an effective host defense against E. coli sepsis observed in previously healthy mice was no longer present in mice with preexisting pancreatitis.CONCLUSIONS:
These data suggest that TLR4 deficiency and acute pancreatitis act similarly in reducing host defense against E. coli peritonitis and that the role of TLR4 in severe Gram-negative infection depends, at least in part, on the presence of preexisting critical illness.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatitis
/
Peritonitis
/
Membrane Glycoproteins
/
Receptors, Cell Surface
/
Sepsis
/
Escherichia coli Infections
Limits:
Animals
Language:
En
Journal:
Crit Care Med
Year:
2005
Document type:
Article
Affiliation country:
Netherlands