Lipopolysaccharide preconditioning and cross-tolerance: the induction of protective mechanisms for rat intestinal ileus.
OBJECTIVE
Endotoxin elicits an inflammatory response within the intestinal muscularis and causes intestinal muscle dysfunction. Our aims were to investigate intestinal muscle recovery after a single or repeated lipopolysaccharide (LPS) injections. We also investigated the ability of LPS to induce cross-tolerance to postoperative ileus.


METHODS
Motility was measured in vivo and in vitro by transit and organ-bath techniques. Nuclear factor kappa-B, nuclear factor interleukin 6, and signal transducer and activator of transcription were quantified by using electrophoretic mobility shift assay, and tumor necrosis factor alpha, interleukin 6, inducible nitric oxide synthase, and cyclooxygenase 2 were measured with reverse-transcription polymerase chain reaction. Myeloperoxidase histochemistry for neutrophils was performed in jejunal muscularis whole mounts.


RESULTS
Endotoxin-induced suppression of in vitro muscle contractility temporally recovered over 7 days with a similar profile whether after a single dose or during the continuous daily injection of LPS. Functional adaptation to continuous LPS was reflected in a significant blunting of transcription factor activation and cytokine messenger RNA up-regulation compared with the naive LPS-stimulated muscularis. Preconditioning of the muscularis showed significant cross-tolerance to the functional, molecular, and leukocytic sequelae of intestinal manipulation.


CONCLUSIONS
The muscularis externa recovered and developed tolerance to endotoxin over 7 days, which conferred cross-tolerance to intestinal manipulation. Thus, preconditioning induces protective mechanisms to a subsequent insult within the muscularis externa.
Schwarz
Nicolas T
NT
Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, USA.
Engel
Britta
B
Eskandari
Mark K
MK
Kalff
Jörg C
JC
Grandis
Jennifer R
JR
Bauer
Anthony J
AJ
D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000235:genetics; D005769:Gastrointestinal Motility / Q000187:drug effects; D007415:Intestinal Obstruction / Q000517:prevention & control*; D007422:Intestines / Q000187:drug effects*; D007527:Isoenzymes / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011183:Postoperative Complications / Q000517:prevention & control*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D022782:CCAAT-Enhancer-Binding Protein-beta; D016207:Cytokines; D007527:Isoenzymes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases