title: Bile mediates intestinal pathology in endotoxemia in rats.
abstract: Intestinal pathology frequently accompanies experimental endotoxic shock and is mediated by proinflammatory cytokines. Our hypotheses are that hepatobiliary factors operating from the luminal side of the gut make a major contribution to this damage and that tumor necrosis factor alpha (TNF-alpha) is involved in the pathology. We treated rats with lipopolysaccharide (LPS) intravenously and found that external drainage of bile totally protected the gastrointestinal tract, macroscopically and microscopically, 4 h after LPS administration and dramatically improved survival of the animals for 48 h after LPS administration. The concentration of TNF-alpha in bile increased markedly after LPS administration and was over 30 times higher in bile than in serum. Tissue damage and the biliary TNF-alpha response were abrogated when animals were pretreated with gadolinium chloride to eliminate Kupffer cells. TNF-alpha infusion into the duodenal lumen caused intestinal damage similar to that elicited by intravenous LPS. In rats treated with LPS, survival was significantly increased during the first 36 h in animals given an infusion of anti-TNF-alpha antibody into the duodenum. These results demonstrate that in endotoxemia, intestinal damage is mediated by factors derived from the bile. The findings indicate that luminally acting TNF-alpha contributes to the intestinal damage.
authors.affiliation: School of Microbiology and Immunology, University of New South Wales, Sydney, New South Wales 2052, Australia.
authors.forename: G D
authors.initials: GD
authors.lastname: Jackson
authors.forename: Y
authors.initials: Y
authors.lastname: Dai
authors.forename: W A
authors.initials: WA
authors.lastname: Sewell
mesh_terms: D000417:Albinism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001646:Bile / Q000378:metabolism*; D001652:Bile Ducts / Q000601:surgery; D001681:Biological Assay; D002404:Catheterization; D019446:Endotoxemia / Q000209:etiology / Q000401:mortality / Q000473:pathology*; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology
chemical_list: D000906:Antibodies; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha