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Experimental Colitis Attenuates Development of Toxin-Induced Cholangitis in Rats

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Abstract

Primary sclerosing cholangitis frequently occurs in association with ulcerative colitis. This close association may be due to colitis predisposing patients to bile ductular injury. Therefore, we determined the susceptibility of rats with experimental colitis to toxin-induced cholangitis. Sprague-Dawley rats received 2,4,6-trinitrobenzene-sulfonic-acid (TNBS) or ethanol vehicle intracolonically. Seven days later, rats received either the biliary epithelial cell toxin α-naphthylisothiocyanate (ANIT) or vehicle and were killed 24 hr later. Liver histology, serum biochemistries and tumor-necrosis factor-α (TNF-α), and hepatic interleukin-10 (IL-10) mRNA were determined. TNBS-treated rats showed extensive macroscopic colonic damage and a 10-fold increase in myeloperoxidase activity compared to ethanol-treated controls. ANIT-treated noncolitic rats showed portal inflammation centered on damaged bile ducts (cholangitis), which was markedly attenuated in ANIT-treated colitic rats. Hepatic IL-10 mRNA was twofold higher in colitic compared to noncolitic rats, with no difference in serum TNF-α. In conclusion, experimental colitis attenuates the development of toxin-induced cholangitis in rats, possibly by up-regulating hepatic IL-10 expression.

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REFERENCES

  1. Lee YM, Kaplan MM: Primary sclerosing cholangitis. N Engl J Med 332(14):924–33, 1995

    PubMed  Google Scholar 

  2. Wiesner RH, Grambsch PM, Dickson ER, Ludwig J, MacCarty RL, Hunter EB, Fleming TR, Fisher LD, Beaver SJ, LaRusso NF: Primary sclerosing cholangitis: Natural history, prognostic factors and survival analysis. Hepatology 10(4):430–436, 1989

    PubMed  Google Scholar 

  3. Farrant JM, Hayllar KM, Wilkinson ML, Karani J, Portmann BC, Westaby D, Williams R: Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology 100(6):1710–1717, 1991

    PubMed  Google Scholar 

  4. Porayko MK, LaRusso NF, Wiesner RH: Primary sclerosing cholangitis: A progressive disease? Semin Liver Dis 11(1):18–25, 1991

    PubMed  Google Scholar 

  5. Olsson R, Danielsson A, Jarnerot G, Lindstrom E, Loof L, Rolny P, Ryden BO, Tysk C, Wallerstedt S: Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis. Gastroenterology 100(5 Pt 1):1319–1323, 1991

    PubMed  Google Scholar 

  6. Wiesner RH, LaRusso NF: Clinicopathologic features of the syndrome of primary sclerosing cholangitis. Gastroenterology 79(2):200–206, 1980

    PubMed  Google Scholar 

  7. Chapman RW, Arborgh BA, Rhodes JM, Summerfield JA, Dick R, Scheuer PJ, Sherlock S: Primary sclerosing cholangitis: A review of its clinical features, cholangiography, and hepatic histology. Gut 21(10):870–877, 1980

    PubMed  Google Scholar 

  8. Schrumpf E, Fausa O, Kolmannskog F, Elgio K, Ritland S, Gjone E: Sclerosing cholangitis in ulcerative colitis. A follow-up study. Scand J Gastroenterol 17(1):33–39, 1982

    PubMed  Google Scholar 

  9. Shepherd HA, Selby WS, Chapman RW, Nolan D, Barbatis C, McGee JO, Jewell DP: Ulcerative colitis and persistent liver dysfunction. Q J Med 52(208):503–513, 1983

    PubMed  Google Scholar 

  10. Das KM, Vecchi M, Sakamaki S: A shared and unique epitope(s) on human colon, skin, and biliary epithelium detected by a monoclonal antibody. Gastroenterology 98(2):464–469, 1990

    PubMed  Google Scholar 

  11. Mandal A, Dasgupta A, Jeffers L, Squillante L, Hyder S, Reddy R, Schiff E, Das KM: Autoantibodies in sclerosing cholangitis against a shared peptide in biliary and colon epithelium. Gastroenterology 106(1):185–192, 1994

    PubMed  Google Scholar 

  12. Wiesner RH: Current concepts in primary sclerosing cholangitis. Mayo Clin Proc 69(10):969–982, 1994

    PubMed  Google Scholar 

  13. Lindor KD, Wiesner RH, MacCarty RL, Ludwig J, LaRusso NF: Advances in primary sclerosing cholangitis. Am J Med 89(1):73–80, 1990

    PubMed  Google Scholar 

  14. Chapman RW: Role of immune factors in the pathogenesis of primary sclerosing cholangitis. Semin Liver Dis 11(1):1–4, 1991

    Google Scholar 

  15. Rask-Madsen J, Hammersgaard EA, Knudsen E: Rectal electrolyte transport and mucosal permeability in ulcerative colitis and Crohn's disease. J Lab Clin Med 81(3):342–353, 1973

    PubMed  Google Scholar 

  16. Seidman EG, Hanson DG, Walker WA: Increased permeability to polyethylene glycol 4000 in rabbits with experimental colitis. Gastroenterology 90(1):120–126, 1986

    PubMed  Google Scholar 

  17. Neilly PJ, Gardiner KR, Kirk SJ, Jennings G, Anderson NH, Elia M, Rowlands BJ: Endotoxaemia and cytokine production in experimental colitis. Br J Surg 82(11):1479–1482, 1995

    PubMed  Google Scholar 

  18. Kawaguchi T, Sakisaka S, Mitsuyama K, Harada M, Koga H, Taniguchi E, Sasatomi K, Kimura R, Ueno T, Sawada N, Mori M, Sata M: Cholestasis with altered structure and function of hepatocyte tight junction and decreased expression of canalicular multispecific organic anion transporter in a rat model of colitis. Hepatology 31(6):1285–1295, 2000

    PubMed  Google Scholar 

  19. Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL: Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96(3):795–803, 1989

    PubMed  Google Scholar 

  20. Roth RA, Dahm LJ: Neutrophil-and glutathione-mediated hepatotoxicity of alpha-naphthylisothiocyanate. Drug Metab Rev 29(1–2):153–165, 1997

    PubMed  Google Scholar 

  21. Bradley PP, Priebat DA, Christensen RD, Rothstein G: Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 78(3):206–209, 1982

    PubMed  Google Scholar 

  22. McHugh KJ, Weingarten HP, Keenan C, Wallace JL, Collins SM: On the suppression of food intake in experimental models of colitis in the rat. Am J Physiol 264(5 Pt 2):R871–R876, 1993

    PubMed  Google Scholar 

  23. He W, Fong Y, Marano MA, Gershenwald JE, Yurt RW, Moldawer LL, Lowry SF: Tolerance to endotoxin prevents mortality in infected thermal injury: Association with attenuated cytokine responses. J Infect Dis 165(5):859–864, 1992

    PubMed  Google Scholar 

  24. Calcamuggi G, Lanzio M, Dughera L, Babini G, Emanuelli G: Endotoxin tolerance and polymyxin B modify liver damage and cholestasis induced by a single dose of alpha-naphthylisothiocyanate in the rat. Arch Toxicol 66(2):126–130, 1992

    PubMed  Google Scholar 

  25. Louis H, Le Moine O, Peny MO, Quertinmont E, Fokan D, Goldman M, Deviere J: Production and role of interleukin-10 in concanavalin A-induced hepatitis in mice. Hepatology 25(6):1382–1389, 1997

    PubMed  Google Scholar 

  26. Tjandra K, Sharkey KA, Swain MG: Progressive development of a Th1-type hepatic cytokine profile in rats with experimental cholangitis. Hepatology 31(2):280–290, 2000

    PubMed  Google Scholar 

  27. Swain MG, Appleyard C, Wallace J, Wong H, Le T: Endogenous glucocorticoids released during acute toxic liver injury enhance hepatic IL-10 synthesis and release. Am J Physiol 276(1 Pt 1):G199–G205, 1999

    PubMed  Google Scholar 

  28. Fausa O, Schrumpf E, Elgio K: Relationship of inflammatory bowel disease and primary sclerosing cholangitis. Semin Liver Dis 11(1):31–39, 1991

    PubMed  Google Scholar 

  29. Lillemoe KD, Pitt HA, Cameron JL: Primary sclerosing cholangitis. Surg Clin North Am 70(6):1381–1402, 1990

    PubMed  Google Scholar 

  30. Cangemi JR, Wiesner RH, Beaver SJ, Ludwig J, MacCarty RL, Dozois RR, Zinsmeister AR, LaRusso NF: Effect of proctocolectomy for chronic ulcerative colitis on the natural history of primary sclerosing cholangitis. Gastroenterology 96(3):790–794, 1989

    PubMed  Google Scholar 

  31. Brand HS, Maas MA, Bosma A, Van Ketel RJ, Speelman P, Chamuleau RA: Experimental colitis in rats induces low-grade endotoxinemia without hepatobiliary abnormalities. Dig Dis Sci 39(6):1210–1215, 1994

    PubMed  Google Scholar 

  32. Weidenbach H, Leiz S, Nussler AK, Dikopoulos N, Bachem M, Buttenschoen K, Reinshagen M, Beger HG, Adler G, Schmid RM: Disturbed bile secretion and cytochrome P450 function during the acute state of experimental colitis in rats. J Hepatol 32(5):708–717, 2000

    PubMed  Google Scholar 

  33. Lora L, Mazzon E, Martines D, Fries W, Muraca M, Martin A, d'Odorico A, Naccarato R, Citi S: Hepatocyte tight-junctional permeability is increased in rat experimental colitis. Gastroenterology 113(4):1347–1354, 1997

    PubMed  Google Scholar 

  34. Kossor DC, Goldstein RS, Ngo W, DeNicola DB, Leonard TB, Dulik DM, Meunier PC: Biliary epithelial cell proliferation following alpha-naphthylisothiocyanate (ANIT) treatment: relationship to bile duct obstruction. Fundam Appl Toxicol 26(1):51–62, 1995

    PubMed  Google Scholar 

  35. Jean PA, Roth RA: Naphthylisothiocyanate disposition in bile and its relationship to liver glutathione and toxicity. Biochem Pharmacol 50(9):1469–1474, 1995

    PubMed  Google Scholar 

  36. Schrumpf E, Elgio K, Fausa O, Gjone E, Kolmannskog F, Ritland S: Sclerosing cholangitis in ulcerative colitis. Scand J Gastroenterol 15(6):689–697, 1980

    PubMed  Google Scholar 

  37. Hobson CH, Butt TJ, Ferry DM, Hunter J, Chadwick VS, Broom MF: Enterohepatic circulation of bacterial chemotactic peptide in rats with experimental colitis. Gastroenterology 94(4):1006–1013, 1988

    PubMed  Google Scholar 

  38. Howard M, O'Garra A: Biological properties of interleukin 10. Immunol Today 13(6):198–200, 1992

    PubMed  Google Scholar 

  39. Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W: Interleukin-10-deficient mice develop chronic enterocolitis [see comments]. Cell 75(2):263–274, 1993

    PubMed  Google Scholar 

  40. Kucharzik T, Stoll R, Lugering N, Domschke W: Circulating antiinflammatory cytokine IL-10 in patients with inflammatory bowel disease (IBD). Clin Exp Immunol 100(3):452–456, 1995

    PubMed  Google Scholar 

  41. Nielsen OH, Koppen T, Rudiger N, Horn T, Eriksen J, Kirman I: Involvement of interleukin-4 and-10 in inflammatory bowel disease. Dig Dis Sci 41(9):1786–1793, 1996

    PubMed  Google Scholar 

  42. Schreiber S, Heinig T, Thiele HG, Raedler A: Immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease. Gastroenterology 108(5):1434–1444, 1995

    PubMed  Google Scholar 

  43. Tagore A, Gonsalkorale WM, Pravica V, Hajeer AH, McMahon R, Whorwell PJ, Sinnott PJ, Hutchinson IV: Interleukin-10 (IL-10) genotypes in inflammatory bowel disease. Tissue Antigens 54(4):386–390, 1999

    PubMed  Google Scholar 

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  1. Liver Unit, Gastrointestinal Research Group, University of Calgary, Calgary, Alberta, Canada, T2N 4N1

    Kartika Tjandra, Tai Le & Mark G. Swain

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  1. Kartika Tjandra
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  2. Tai Le
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Tjandra, K., Le, T. & Swain, M.G. Experimental Colitis Attenuates Development of Toxin-Induced Cholangitis in Rats. Dig Dis Sci 47, 1216–1223 (2002). https://doi.org/10.1023/A:1015330809095

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