title: Endogenous endotoxin participates in causing a panenteric inflammatory ileus after colonic surgery.
abstract: OBJECTIVE
  To investigate muscularis inflammation and endogenous endotoxin as causes of postoperative ileus.
  
  
  BACKGROUND
  Postoperative inflammatory ileus of the colon is associated with a significant delay in gastrointestinal transit. We investigated whether these changes are caused by the downstream obstructive barrier of the surgically altered colon or by small intestinal muscularis inflammation itself. Furthermore, we evaluated the mechanistic role of gut derived endotoxin in the development of postoperative intestinal dysfunction.
  
  
  METHODS
  Rats underwent surgical manipulation of the colon. Isolated gastrointestinal transit was analyzed in animals with ileostomy. The perioperative emigration of intracolonic particles was investigated by colonic luminal injection of fluorescently labeled LPS and microspheres. Mediator mRNA induction was quantified by real-time RT-PCR. Muscularis leukocytic infiltrates were characterized. In vitro circular muscle contractility was assessed in a standard organ bath.
  
  
  RESULTS
  Ileostomy rats presented with a significant delay in small intestinal transit after colonic manipulation. This was associated with leukocyte recruitment and inflammatory mediator mRNA induction within the small intestinal muscularis. Colonic manipulation caused the transference of intracolonic LPS and microspheres into the intestinal muscularis. Postoperative in vitro small intestinal circular muscle contractility was impaired by 42% compared with controls. Gut decontamination and TLR-4 deletion significantly alleviated the small intestinal muscularis inflammation and prevented intestinal muscle dysfunction.
  
  
  CONCLUSIONS
  Selective colonic manipulation initiates a distant inflammatory response in the small intestinal muscularis that contributes to postoperative ileus. The data provide evidence that gut-derived bacterial products are mechanistically involved in the initiation of this remote inflammatory cascade.
authors: Department of Medicine, Division of Gastroenterology, University of Pittsburgh Medical Center, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
authors: Andreas
authors: A
authors: Türler
authors: Christoph
authors: C
authors: Schnurr
authors: Atsunori
authors: A
authors: Nakao
authors: Sandra
authors: S
authors: Tögel
authors: Beverley A
authors: BA
authors: Moore
authors: Noriko
authors: N
authors: Murase
authors: Jörg C
authors: JC
authors: Kalff
authors: Anthony J
authors: AJ
authors: Bauer
mesh_terms: D000818:Animals; D003106:Colon / Q000601:surgery*; D004731:Endotoxins / Q000502:physiology*; D004751:Enteritis / Q000209:etiology*; D004926:Escherichia coli; D005772:Gastrointestinal Transit / Q000502:physiology*; D045823:Ileus / Q000209:etiology*; D018836:Inflammation Mediators / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology*; D008297:Male; D009092:Mucous Membrane / Q000378:metabolism; D009130:Muscle, Smooth / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000502:physiology
chemical_list: D004731:Endotoxins; D018836:Inflammation Mediators