Abstract
To test the hypothesis that endotoxin is absorbed from the gut into the circulation in rats with experimental acute pancreatitis we studied two different animal models. In the first model necrotizing pancreatitis was induced by the ligation of the disatl bilio‐pancreatic duct while in the second, experimental oedematous acute pancreatitis was induced by subcutaneous injections of caerulein. In both experiments, in the colon of rats with acute pancreatitis endotoxin from Salmonella abortus equi was injected. Endotoxin was detected by immunohistochemistry in peripheral organs with specific antibodies. The endotoxin was found only in rats with both acute pancreatitis and endotoxin injected into the colon and not in the control groups. The distribution of endotoxin in liver at 3 and 5 days was predominantly at hepatocytes level around terminal hepatic venules, while in lung a scattered diffuse pattern at the level of alveolar macrophages was identified. A positive staining was observed after 12 hours in the liver, lung, colon and mesenteric lymph nodes of rats with both caerulein pancreatitis and endotoxin injected into the colon. We conclude that the experimental acute pancreatitis leads to early endotoxin translocation from the gut lumen in the intestinal wall and consequent access of gut‐derived endotoxin to the mesenteric lymph nodes, liver and lung.
Keywords: pancreatitis, gut‐derived endotoxin, caerulein
References
- 1. Beger H.G., Bittner R., Büchler M., Bacterial contamination of pancreatic necrosis. Gastroenterology, 91: 433–488, 1986. [DOI] [PubMed] [Google Scholar]
- 2. Wig J.D., Kochhar R., Ray J.D., Krishna Rao D.V., Gupta N.M., Ganguly N.K., Endotoxemia predicts outcome in acute pancreatitis. J. Clin. Gastroenterol., 26: 121–124, 1998. [DOI] [PubMed] [Google Scholar]
- 3. Ammori B.J., Leeder P.C., King R.F., Barclay G.R., Martin I.G., Larvin M., McMahon M.J., Early increase in intestinal permeability in patients with severe acute pancreatitis: correlation with endotoxemia, organ failure, and mortality, J. Gastrointest. Surg., 3: 252–262, 1999. [DOI] [PubMed] [Google Scholar]
- 4. Deventer S.J.H., Ten Cate J.W., Tytgat G.N.J., Intestinal endotoxemia. Clinical significance. Gastroenterology, 94: 825, 1988. [DOI] [PubMed] [Google Scholar]
- 5. Tani S., Experimental acute pancreatitis induced by excessive doses of caerulein in rats; protective and therapeutic effects of trypsin inhibitor urinastatin and CCK receptor antagonist CR 1392. Kobe J. Med. Sci., 34: 93, 1988. [PubMed] [Google Scholar]
- 6. Luiten E.J.T., Hop W.C.J., Lange J.F., Bruining H.A., Controlled clinical trial of selective decontamination for the treatment of severe acute pancreatitis. Ann. Surg., 222: 57, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Wilson C. and Imrie C.W., Systemic effects of acute pancreatitis, In: Johnson C.D. and Imrie C.W., eds., Pancreatic Disease. Progress and Prospects, Springer Verlag, Heidelberg , New York , Paris , 1993, pp. 287–297. [Google Scholar]
- 8. Ohlsson K. and Genell S., Pathophysiology of acute pancreatitis In: Johnson C.D. and Imrie C.W., eds., Pancreatic Disease. progress and Prospects, Springer Verlag, Heidelberg , New York , Paris , 1993, pp. 213–226. [Google Scholar]
- 9. Poos R.J. and Beger H.G., Bacterial toxins in ascites and blood in patients with acute pancreatitis In: Beger H.G. and Büchler M., eds., Acute pancreatitis, Springer Verlag, Heidelberg , New York , Paris , 1987, pp. 201–206. [Google Scholar]
- 10. Wilson P.G., Manji M., Neoptolemos J.P., Acute pancreatitis as a model of sepsis. J. Antimicrob. Chemother., 41: Suppl A: 51–63, 1998. [DOI] [PubMed] [Google Scholar]
- 11. Marotta F., Geng T.C., Wu C.C., Barbi G., Bacterial translocation in the course of acute pancreatitis: beneficial role of nonabsorbable antibiotics and lactitol enemas, Digestion, 57: 446–452, 1996. [DOI] [PubMed] [Google Scholar]
- 12. Gianotti L., Solomkin J.S., Munda R., Alexander J.W., Failure of local and systemic bacterial clearance in rats with acute pancreatitis, Pancreas, 10: 78–84, 1995. [DOI] [PubMed] [Google Scholar]
- 13. Gianotti L., Munda R., Alexander J.W., Tchervenkov J.L., Babcock G.F., Bacterial translocation: a potential source for infection in acute pancreatitis. Pancreas, 8: 551, 1993. [PubMed] [Google Scholar]
- 14. De Beaux A.C., Fearon K.C., Circulating endotoxin, tumour necrosis factor‐alpha, and their natural antagonists in the pathophysiology of acute pancreatitis, Scand. J. Gastroenterol., (Suppl)., 219: 43–46, 1996. [DOI] [PubMed] [Google Scholar]
- 15. Tani S., Otsuki M., Itoh H., Fujii M., Nakamura T., Oka T., Baba S., Histologic and biochemical alterations in experimental acute pancreatitis induced by supramaximal caerulein stimulation. Int. J. Pancreatol., 2: 337, 1987. [DOI] [PubMed] [Google Scholar]
- 16. Medich D.S., Lee T.K., Melhem M.K., Rowe M.I., Schraut WS, Lee KKW., Pathogenesis of pancreatic sepsis.. Am. J. Surg., 165: 46, 1993. [DOI] [PubMed] [Google Scholar]
- 17. Gianotti L., Munda R., Gennari R., Pyles T., Alexander J.W., Effect of different regimens of gut decontamination on bacterial translocation and mortality in experimental acute pancreatitis. Eur. J. Surg., 161: 85, 1995. [PubMed] [Google Scholar]
- 18. Gianotti L., Munda R., Alexander J.W., Pancreatitis induced microbial translocation: a study of the mechanisms. Res. Surg., 4: 87, 1992. [Google Scholar]
- 19. Vaccaro M.I., Calvo E.L., Suburo A.M., Sordelli D.O., Lanosa G., Iovanna J.L., Lipopolysaccharide directly affects pancreatic acinar cells: implications on acute pancreatitis pathophysiology, Dig. Dis. Sci., 45: 915–926, 2000. [DOI] [PubMed] [Google Scholar]
- 20. Jiang J., Bahrami S., Leichtfried G., Redl H., Öhlinger W., Schlag G., Kinetics of endotoxin and tumor necrosis factor appearance in portal and systemic circulation after hemorrhagic shock in rats. Ann. Surg., 221: 100, 1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Welbourne C.R.B., Wise W.C., Endotoxin, septic shock and acute lung injury: neutrophils, macrophages and inflammatory mediators. Br. J. Surg., 79: 998, 1992. [DOI] [PubMed] [Google Scholar]