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Infection and Immunity, August 2000, p. 4714-4719, Vol. 68, No. 8
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Bile Mediates Intestinal Pathology in Endotoxemia in Rats

Graham D. F. Jackson,1,dagger Yung Dai,1 and William A. Sewell2,*

School of Microbiology and Immunology, University of New South Wales, Sydney, New South Wales 2052,1 and Centre for Immunology, University of New South Wales and St. Vincent's Hospital, Sydney, New South Wales 2010,2 Australia

Received 31 January 2000/Returned for modification 25 February 2000/Accepted 15 March 2000

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.

* Corresponding author. Mailing address: Centre for Immunology, St. Vincent's Hospital Sydney, Darlinghurst, NSW 2010, Australia. Phone: 61 2 9361 7700. Fax: 61 2 9361 2391. E-mail: w.sewell{at}cfi.unsw.edu.au.

dagger Graham Jackson made a major contribution to this project prior to his death on 6 June 1997.

Infection and Immunity, August 2000, p. 4714-4719, Vol. 68, No. 8
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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