Digestive Diseases and Sciences

, Volume 49, Issue 4, pp 556–564 | Cite as

Impact of Dextran Sulfate Sodium Load on the Severity of Inflammation in Experimental Colitis

  • Thorsten Vowinkel
  • Theodore J. Kalogeris
  • Mikiji Mori
  • Christian F. Krieglstein
  • D. Neil Granger
Article

Abstract

In dextran sulfate sodium (DSS)-induced inflammatory bowel disease in mice the relationship between the amount of ingested DSS and the severity of colitis has not been systematically investigated. We examined whether (1) the severity of colitis is DSS load-dependent, and (2) there is a critical DSS load required to reliably induce colitis. DSS load was calculated as: (drinking volume (ml) × [DSS (g)/100 ml])/body weight (g). A minimum DSS load ≥ 30 mg/g body weight over 7 days resulted in a significantly elevated colonic myeloperoxidase (MPO) activity, compared to mice receiving less DSS and controls (P < 0.05). Histomorphologic data correlated with MPO activity and revealed significantly higher damage scores once the DSS load was ≥ 30 mg/g body weight. Our findings demonstrate the importance of monitoring DSS load in this model of experimental colitis.

dextran sulfate sodium inflammatory bowel disease disease activity index myeloperoxidase assay histology 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Arndt H, Kubes P, Grisham MB, Gonzalez E, Granger DN: Granulocyte turnover in the feline intestine. Inflammation 16:549-559, 1992Google Scholar
  2. 2.
    Axelsson LG, Landstroem E, Goldschmidt TJ, Groenberg A, Bylund-Fellenius AC: Dextran sulfate sodium (DSS) induced experimental colitis in immunodeficient mice: Effects in CD4+-cell depleted, athymic and NK-cell depleted SCID mice. Inflamm Res 45:181-191, 1996Google Scholar
  3. 3.
    Axelsson L, Landstroem E, Lundberg C, Bylund-Fellenius A: The degree of sulfate content and the molecular weight of dextran sulfate and carageenan are important for the induction of colitis in mice. Gastroenterology 110:A585, 1996 (abstract)Google Scholar
  4. 4.
    Bauer P, Russel JM, Granger DN: Role of endotoxin in intestinal reperfusion-induced expression of E-selectin. Am J Physiol Gastrointest Liver Physiol 276:G479-G484, 1999Google Scholar
  5. 5.
    Blumberg RS, Saubermann LJ, Strober W: Animal models of mucosal inflammation and their relation to human inflammatory bowel disease. Curr Opin Immunol 11:648-656, 1999Google Scholar
  6. 6.
    Boismenu R, Chen Y, Chou K, El-Sheikh A, Buelow R: Orally administered RDP58 reduces the severity of dextran sodium sulphate induced colitis. Ann Rheum Dis 61(Suppl II):19-24, 2002Google Scholar
  7. 7.
    Cooper HS, Murthy SNS, Shah RS, Sedergran DJ: Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 69:238-249, 1993Google Scholar
  8. 8.
    Dieleman LA, Ridwan BU, Tennyson GS, Beagley KW, Bucy RP, Elson CO: Dextran sulfate sodium-induced colitis occurs in severe combined immunodeficient mice. Gastroenterology 107:1643-1652, 1994Google Scholar
  9. 9.
    Dieleman LA, Palmen MJ, Akol H, Bloemena E, Pena AS, Meuwissen SG, Van Rees EP: Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol 114:385-391, 1998Google Scholar
  10. 10.
    Ebaugh FG: Quantitative measurement of gastrointestinal blood loss. J Lab Clin Med 53:77, 1959Google Scholar
  11. 11.
    Egger B, Bajaj-Elliott M, MacDonald TT, Inglin R, Eysselein VE, Buechler MW: Characterization of acute murine dextran sodium sulphate colitis: Cytokine profile and dose dependency. Digestion 62:240-248, 2000Google Scholar
  12. 12.
    Elson CO, Sartor RB, Tennyson GS, Riddel RH: Experimental models of inflammatory bowel disease. Gastroenterology 109:1344-1367, 1995Google Scholar
  13. 13.
    Farkas S, Herfarth H, Roesle M, Schroeder J, Steibauer M, Guba M, Beham A, Schoelmerich J, Jauch KW, Anthuber M: Quantification of mucosal leukocyte endothelial cell interaction by in vivo fluorescence microscopy in experimental colitis in mice. Clin Exp Immunol 126:250-256, 2001Google Scholar
  14. 14.
    Fiocchi C: Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 115:182-205, 1998Google Scholar
  15. 15.
    Foca A, Nicoletta P, Matera G, Mastroeni P, Caputi AP: Antidipsogenic effect of endotoxin in the rat. Circ Shock 11:341-350, 1983Google Scholar
  16. 16.
    Ganesan R, Summers C: Glucocorticoids potentiate the dipsogenic action of angiotensin II. Brain Res 499:121-130, 1989Google Scholar
  17. 17.
    Hamamoto N, Maemura K, Hirata I, Murano M, Sasaki S, Katsu K: Inhibition of dextran sulphate sodium (DSS)-induced colitis in mice by intracolonically administered antibodies against adhesion molecules (endothelial leucocyte adhesion molecule-1 (ELAM-1) or intercellular adhesion molecule-1 (ICAM-1)). Clin Exp Immunol 117:462-468, 1999Google Scholar
  18. 18.
    Iizasa H, Genda N, Kitano T, Tomita M, Nishihara K, Hayashi M, Nakamura K, Kobayashi S, Nakashima E: Altered expression and function of p-glycoprotein in dextran sodium sulfate-induced colitis in mice. J Pharm Sci 92:569-576, 2003Google Scholar
  19. 19.
    Iwanaga T, Hoshi O, Han H, Fujita T: Morphological analysis of acute ulcerative colitis experimentally induced by dextran sulphate sodium in the guinea pig: some possible mechanisms of caecal ulceration. J Gastroenterol 29:430-438, 1994Google Scholar
  20. 20.
    Jeffers M, McDonald WF, Chillakuru RA, Yang M, Nakase H, Deegler LL, Sylander ED, Rittman B, Bendele A, Sartor RB, Lichtenstein HS: A novel human fibroblast growth factor treats experimental intestinal inflammation. Gastroenterology 123:1151-1162, 2002Google Scholar
  21. 21.
    Kitajima S, Takuma S, Morimoto M: Tissue distribution of dextran sulfate sodium in the acute phase of murine DSS-induced colitis. J Vet Med Sci 61:67-70, 1999Google Scholar
  22. 22.
    Kitajima S, Takuma S, Morimoto M: Histological analysis of murine colitis induced by dextran sulfate sodium of different molecular weights. Exp Anim 49:9-15, 2000Google Scholar
  23. 23.
    Krawisz JE, Sharon P, Stenson WF: Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology 87:1344-1350, 1984Google Scholar
  24. 24.
    Krieglstein CF, Cerwinka WH, Laroux FS, Grisham MB, Schuermann G, Bruewer M, Granger DN: Role of appendix and spleen in experimental colitis. J Surg Res 101:166-175, 2001Google Scholar
  25. 25.
    Krieglstein CF, Cerwinka WH, Laroux FS, Salter JW, Russell JM, Schuermann G, Grisham MB, Ross CR, Granger DN: Regulation of murine intestinal inflammation by reactive metabolites of oxygen and nitrogen: divergent roles of superoxide and nitric oxide. J Exp Med 194:1207-1218, 2001Google Scholar
  26. 26.
    Krieglstein CF, Cerwinka WH, Sprague AG, Laroux FS, Grisham MB, Koteliansky VE, Senninger N, Granger DN, Fougerolles AR: Collagen-binding integrin α1β1 regulates intestinal inflammation in experimental colitis. J Clin Invest 110:1773-1782, 2002Google Scholar
  27. 27.
    Kruidenier L, van Meeteren ME, Kuiper I, Jaarsma D, Lamers CB, Zijlstra FJ, Verspaget HW: Attenuated mild colonic inflammation and improved survival from severe DSS-colitis of transgenic Cu/Zn-SOD mice. Free Radic Biol Med 34:753-765, 2003Google Scholar
  28. 28.
    Liu Q, Wang Y, Wan MX, Zhang XW, Andersson G, Hedlund G, Thorlacius H: Roquinimex inhibits dextran sodium sulfate-induced murine colitis. Inflamm Res 52:64-68, 2003Google Scholar
  29. 29.
    Logan RF: Inflammatory bowel disease incidence: up, down or unchanged? Gut 42:309-311, 1998Google Scholar
  30. 30.
    Mabley JG, Pacher P, Liaudet L, Soriano FG, Hasko G, Marton A, Szabo C, Salzman AL: Inosine reduces inflammation and improves survival in a murine model of colitis. Am J Physiol Gastrointest Liver Physioil 284:G138-G144, 2003Google Scholar
  31. 31.
    Maehler M, Bristol IJ, Leiter EH, Workman AE, Birkenmeier EH, Elson CO, Sundberg JP: Differential susceptibility of inbred mouse strains to dextran sulfate sodium-induced colitis. Am J Physiol Gastrointest Liver Physiol 274:G544-G551, 1998Google Scholar
  32. 32.
    Maehler M, Bristol IJ, Sundberg JP, Churchill GA, Birkenmeier EH, Elson CO, Leiter EH: Genetic analysis of susceptibility to dextran sulfate sodium-induced colitis in mice. Genomics 55:147-156, 1999Google Scholar
  33. 33.
    Mombaerts P, Mizoguchi E, Grusby MJ, Glimcher LH, Bhan AK, Tonegawa S: Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell 75:275-282, 1993Google Scholar
  34. 34.
    Myers KJ, Murthy S, Flanigan A, Witchell DR, Butler M, Murray S, Siwkowski A, Goodfellow D, Madsen K, Baker B: Antisense oligonucleotide blockade of tumor necrosis factor-α in two murine models of colitis. J Pharmacol Exp Ther 304:411-424, 2003Google Scholar
  35. 35.
    Naito Y, Takagi T, Ishikawa T, Handa O, Matsumoto N, Yagi N, Matsuyama K, Yoshida N, Yoshikawa T, Kotake Y. α-Phenyl-N-tert-Butylnitrone provides protection from dextran sulfate sodium-induced colitis in mice. Antioxid Redox Signal 4:195-206, 2002Google Scholar
  36. 36.
    Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R: A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98:694-702, 1990Google Scholar
  37. 37.
    Osaka T, Kannan H, Kawano S, Ueta Y, Yamashita H: Intraperitoneal administration of recombinant human interleukin-1 beta inhibits osmotic thurst in the rat. Physiol Behav 51:1267-1270, 1992Google Scholar
  38. 38.
    Perez Guaita MF Chiaraviglio E: Effect of prostaglandin E1 and its biosynthesis inhibitor indomethacin on drinking in the rat. Pharmacol Biochem Behav 13:787-792, 1980Google Scholar
  39. 39.
    Sartor RB, Bender DE, Holt LC: Susceptibility of inbred rat strains to intestinal inflammation induced by indomethacin. Gastroenterology 102:A690, 1992 (abstract)Google Scholar
  40. 40.
    Sasaki M, Bharwani S, Jordan P, Joh T, Manas K, Warren A, Harada H, Carter P, Elrod JW, Wolcott M, Grisham MB, Alexander JS: The 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor pravastatin reduces disease activity and inflammation in dextran sulfate induced colitis. J Pharmacol Exp Ther 305:78-85, 2003Google Scholar
  41. 41.
    Siegmund B, Lehr HA, Fantucci G: Leptin: a pivotal mediator of intestinal inflammation in mice. Gastroenterology 122:2011-2025, 2002Google Scholar
  42. 42.
    Sivakumar PV, Westrich GM, Kanaly S, Garka K, Born TL, Derry JMJ, Vilney JL: Interleukin 18 is a primary mediator of the inflammation associated with dextran sulphate sodium induced colitis: blocking interleukin 18 attenuates intestinal damage. Gut 50:812-820, 2002Google Scholar
  43. 43.
    Strober W: Animal models in inflammatory bowel disease—An overview. Dig Dis Sci 12:3S-10S, 1985Google Scholar
  44. 44.
    Tamaru T, Kobayashi H, Kishimoto S, Kajiyama G, Shimamoto F, Brown WR: Histochemical study of colonic cancer in experimental colitis of rats. Dig Dis Sci 38:529-537, 1993Google Scholar
  45. 45.
    Wan MX, Riaz AA, Schramm R, Wang Y, Vestweber D, Menger MD, Thorlacius H: Leukocyte rolling is exclusively mediated by P-selectin in colonic venules. Br J Pharmacol 135:1749-1756, 2002Google Scholar
  46. 46.
    Yamada M, Ohkusa T, Okayasu I: Occurrence of dysplasia and adenocarcinoma after experimental chronic ulcerative colitis in hamsters induced by dextran sulphate sodium. Gut 33:1521-1527, 1992Google Scholar

Copyright information

© Plenum Publishing Corporation 2004

Authors and Affiliations

  • Thorsten Vowinkel
    • 1
    • 2
  • Theodore J. Kalogeris
    • 3
  • Mikiji Mori
    • 1
  • Christian F. Krieglstein
    • 2
  • D. Neil Granger
    • 1
  1. 1.Department of Molecular and Cellular PhysiologyLouisiana State University Health Sciences CenterShreveportUSA
  2. 2.Department of General SurgeryUniversity of MünsterMünsterGermany
  3. 3.Department of SurgeryLouisiana State University Health Sciences CenterShreveportUSA

Personalised recommendations