Inflammation Research

, Volume 45, Issue 4, pp 181–191

Dextran sulfate sodium (DSS) induced experimental colitis in immunodeficient mice: Effects in CD4+-cell depleted, athymic and NK-cell depleted SCID mice

  • L. -G. Axelsson
  • E. Landström
  • T. J. Goldschmidt
  • A. Grönberg
  • A. -C. Bylund-Fellenius
Original Research Papers


Administration of dextran sulfate to mice, given in the drinking water results in acute or subacute colonic inflammation, depending on the administration protocol. This colonic inflammation exhibits ulceration, healing and repair, and a therapeutic response that makes it valuable for the study of mechanisms that could act in the pathogenesis of human ulcerative colitis, a disease thought to have an immunologically dependent pathogenesis. To investigate if immunological mechanisms were involved in the induction of colonic inflammation in this model, mice with different degrees of immunodeficiency were used. It was shown that dextran sulfate induced colitis could be induced in Balb/c mice depleted of CD4+ helper T cells by treatment with monoclonal antibodies preceded by adult thymectomy. The depletion of CD4+ was verified by flow cytometric analysis. Furthermore, the colonic inflammation could equally be induced in athymic CD-1 nu/nu mice lacking thymusderived T cells, in T and B-cell deficient SCID mice, and also in SCID mice depleted of NK cells by treatment with anti-asialo GM1 antibodies. The NK-cell depletion was verified by measuring spleen NK-cell activity. The resulting colonic inflammation in all these types of deficient mice was qualitatively comparable, as shown by clinical and histological appearance. These results indicate that the presence of functional T, B and NK cells is not crucial for the induction of dextran sulfate colitis in mice.


Disease models Mice Immunocompromised Ulcerative colitis Dextran sulfate 


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  1. [1]
    Jewell DP, Chapman RGW, Mortensen N. Ulcerative colitis and Crohn's disease, a clinicians guide. London: Churchill Livingstone, 1992:79.Google Scholar
  2. [2]
    Snook J. Are the inflammatory bowel diseases autoimmune disorders. Gut 1990;31:961–3.Google Scholar
  3. [3]
    Raedler A, Schreiber S. Ist die Colitis ulcerosa eine Autoimmunerkrankung? Dtsch Med Wochenschr 1992;117:1333–8.Google Scholar
  4. [4]
    Brandtzaeg P. Autoimmunity and ulcerative colitis. Can two enigmas make sense together? Gastroenterology 1995;109:307–22.Google Scholar
  5. [5]
    Axelsson LG, Ahlstedt S. Actions of sulphasalazine and analogues in animal models of experimental colitis. Inflammopharmacology 1993;2:219–32.Google Scholar
  6. [6]
    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 1990;98:694–702.Google Scholar
  7. [7]
    Axelsson L-G, Landström E, Bylund-Fellenius A-C. Effects of sulfasalazine on survival of athymic mice with dextran sulfate (DSS) induced colitis. Gut 1992;Suppl 33:S39.Google Scholar
  8. [8]
    Axelsson LG, Landström E, Bylund-Fellenius AC. Sulfasalazine and olsalazine are effective for the treatment of dextran sulfate induced colitis in athymic mice. Gastroenterology 1994;106:648.Google Scholar
  9. [9]
    Kimura I, Kamiya A, Nagahama S, Yoshida J, Tanigawa H, Kataoka M. Study on the experimental ulcerative colitis model induced by dextran sulfate sodium in rats: Estimation of mucosal erosions by the alcian blue-staining method. Folia Pharmacol Jpn 1993;102:343–50.Google Scholar
  10. [10]
    Kimura I, Nagahama S, Kawasaki M, Kamiya A, Kataoka M. Study on the experimental ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) in rats (2). Folia Pharmacol Jpn 1995;105:145–52.Google Scholar
  11. [11]
    Nakamaru K, Sugai K, Hongyo T, Sato M, Taniguchi S, Tanaka Y, et al. Effect of mesalazine microgranules on experimental colitis. Folia Pharmacol Jpn 1994;104:303–10.Google Scholar
  12. [12]
    Zijstra FJ, Garrelds IM, van Dijk APM, Wilson JHP. Experimental colitis in mice: Effects of olsalazine on eicosanoid production in colonic tissue. Agents Actions 1992:C76-8.Google Scholar
  13. [13]
    Greenfield SM, Punchard NA, Teare J-P, Thompson RPH. Review article: the mode of action of the aminosalicylates in inflammatory bowel disease. Aliment Pharmacol Ther 1993;7:369–83.Google Scholar
  14. [14]
    Cooper HS, Murthy SNS, Shah RS, Sedegran DJ. Clincopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 1993;69:238–49.Google Scholar
  15. [15]
    Bylund-Fellenius A-C, Landström E, Axelsson L-G, Midtvedt T. Experimental colitis induced by dextran sulphate in normal and germfree mice. Microb Ecol Health Dis 1994;7:207–15.Google Scholar
  16. [16]
    Buell MG, Merin MC. Neutrophil-independency of the initiation of colonic injury: Comparison of results from three models of experimental colitis in the rat. Dig Dis Sci 1994;39:2575–88.Google Scholar
  17. [17]
    Murthy SNS, Cooper HS, Shim H, Shah RS, Ibrahim SA, Sedergran DJ. Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin. Dig Dis Sci 1993;38:1722–34.Google Scholar
  18. [18]
    Ohkusa T, Yamada M, Takenaga T. Protective effect of metronidazole in experimental ulcerative colitis induced by dextran sulfate sodium. Jpn J Gastroenterol 1987;84:2337–46.Google Scholar
  19. [19]
    Weldon MJ, Maxwell JD. Lymphocyte and macrophage interleukin receptors in inflammatory bowel disease: a more selective target for therapy? Gut 1994;35:867–71.Google Scholar
  20. [20]
    Pierres A, Naquet P, Van Agthoven A, Bekkhoucha F, Denizot F, Mishal Z, et al. A rat anti-mouse T4 monoclonal antibody (H129.19) inhibits the proliferation of Ia-reactive T cell clones and delineates two phenotypically distinct (T4+, Lyt-2,3, and T4, Lyt-2,3+) subsets among anti-Ia cytolytic T cell clones. J Immunol 1984;132:2775–82.Google Scholar
  21. [21]
    Lanier LL, Gutman GA, Lewis DE, Griswold ST, Warner NL. Monoclonal antibodies against rat immunoglobulin kappa chains. Hybridoma 1982;1:125–31.Google Scholar
  22. [22]
    Goldschmidt TJ, Holmdahl R, Klareskog L. Depletion of murine T cells by in vivo monoclonal antibody treatment is enhanced by adding an autologous anti-rat k chain antibody. Journal Immunol Meth 1988;111:219–26.Google Scholar
  23. [23]
    Grönberg A, Kiessling R, Eriksson E, Hansson M. Variants from a MLV-induced lymphoma selected for decreased sensitivity to NK lysis. J Immunol 1981;127:1734–9.Google Scholar
  24. [24]
    Axelsson L-G, Ahlstedt S. A fluorescence method for the visualization of inflammatory cells in intestinal mucosa. J Immunol Methods 1990;127:271–7.Google Scholar
  25. [25]
    Cary NC. SAS/STAT Users Guide. 4th ed, vol 2 SAS Institute Inc., 1989.Google Scholar
  26. [26]
    Ishioka T, Kuwabara N, Oohasi Y, Wakabayashi K. Induction of colorectal tumors in rats by sulfated polysaccharides. CRC Crit Rev Toxicol 1987;17:215–44.Google Scholar
  27. [27]
    Hirono I, Kuhara K, Hosaka S, Tomizawa S, Goldberg L. Induction of intestinal tumors in rats by dextran sulfate sodium. J Natl Cancer Inst 1981;66(7):579–83.Google Scholar
  28. [28]
    Shanahan F. Pathogenesis of ulcerative colitis. Lancet 1993;342:407–11.Google Scholar
  29. [29]
    Guy-Grand D, Vasalli P. Gut intraepithelial T lymphocytes. Curr Opin Immunol 1993;5:247.Google Scholar
  30. [30]
    Hörnqvist E, Goldschmidt T, Holmdahl R, Lycke N. Host defense against cholera toxin is strongly CD4+ T cell dependent. Infect Immun 1991;59:3630–8.Google Scholar
  31. [31]
    Charlton B, Burkhardt K, Mandel TE. How important is the L3T4 antigen to L3T4+ cell function in vivo. Immunol Today 1988;9:165–8.Google Scholar
  32. [32]
    Strober W, Ehrhardt RO. Chronic intestinal inflammation: An unexpected outcome in cytokine or T cell receptor mutant mice. Cell 1993;75:203–5.Google Scholar
  33. [33]
    Macdonald HR, Blanc C, Lees RK, Sordat B. Abnormal distribution of T cell subsets in athymic mice. J Immunol 1986;136:4337–9.Google Scholar
  34. [34]
    Lake JP, Pierce CW, Kennedy JD. T cell receptor expression by T cells that mature extrathymically in nude mice. Cell Immunol 1991;135:259–65.Google Scholar
  35. [35]
    Lake JP, Pierce CW, Kennedy JD. CD8+ α/β or γ/σ T cell receptor-bearing T cells from athymic nude mice are cytolytically active in vivo. J Immunol 1991;147:1121–6.Google Scholar
  36. [36]
    Kikly K, Dennert G. Evidence for extrathymic development of TNK Cells. NK1+ CD3+ cells responsible for acute marrow graft rejection are present in thymus-deficient mice. J Immunol 1992;149:403–12.Google Scholar
  37. [37]
    Rogers HW, Tripp CS, Schreiber RD, Unanue ER. Endogenous IL-1 is required for neutrophil recruitment and macrophage activation during murine Listeriosis. J Immunol 1994;153:2093–101.Google Scholar
  38. [38]
    Coutinho A, Möller G, Richter W. Molecular basis of B-cell activation. I. Mitogenicity of native and substituted dextrans. Scand J Immunol 1974;3:321–38.Google Scholar
  39. [39]
    Gronowicz E, Biberfeld P, Wahren B, Coutinho A. Characterization of dextran-sulfate-sensitive cells. Scand J Immunol 1976;5:573–82.Google Scholar
  40. [40]
    Persson UCI, Hammarström LG, Smith CIE. Macrophages are required for the dextran-sulfate induced activation of B lymphocytes. J Immunol 1977;119:1138–44.Google Scholar
  41. [41]
    Kishimoto S, Kobayashi H, Shimizu S, Haruma K, Tamaru T, Kajiyama G, et al. Changes of colonic vasoactive intestinal peptide and cholinergic activity in rats with chemical colitis. Dig Dis Sci 1992;37:1729–37.Google Scholar
  42. [42]
    Fiebig E, Ley K, Arfors K-E. Rapid leukocyte accumulation by “spontaneous” rolling and adhesion in the exteriorized rabbit mesentery. Int J Microcirc: Clin Exp 1991;10:127–44.Google Scholar
  43. [43]
    Chen Y, Conner EM, Grisham MB. Dextran sodium (DSS)-induces colitis in rats by enhancing mucosal permeability: Effects of sulfasalazine. Gastroenterology 1995;108:796.Google Scholar
  44. [44]
    Chen Y, Grisham MB. Effect of dextran sulfate sodium on the proliferative activity of intestinal crypt epithelial cells. Gastroenterology 1994;106:663.Google Scholar
  45. [45]
    Kamochi M, Ogata M, Yoshida S, Matsumoto T, Kubota E, Mizuguchi Y, et al. Dextran sulphate enhancement of lipopolysaccharide-induced tumour necrosis factor-α production by murine peritoneal macrophages: Correlation with macrophage blockade. FEMS Immunol Med Microbiol 1993;7:153–60.Google Scholar
  46. [46]
    Shnyra A, Lindberg AA. Scavenger receptor pathway for lipopolysaccharide binding to Kupffer and endothelial liver cells in vitro. Infect Immun 1995;63:865–73.Google Scholar
  47. [47]
    Axelsson L-G, Landström E, Bylund-Fellenius A-C, Midtvedt T. Dextran sulfate sodium induced colitis and sulfasalazine treatment in bacteria-free mice. Gastroenterology 1995;108:775.Google Scholar
  48. [48]
    Grimm MC, Pullman WE, Bennett GM, Sullivan PJ, Pavli P, Doe WF. Direct evidence of monocyte recruitment to inflammatory bowel disease mucosa. J Gastroent Hepatol 1995;10:387–95.Google Scholar

Copyright information

© Birkhäuser Verlag 1996

Authors and Affiliations

  • L. -G. Axelsson
    • 1
    • 2
  • E. Landström
    • 2
  • T. J. Goldschmidt
    • 3
  • A. Grönberg
    • 2
  • A. -C. Bylund-Fellenius
    • 4
  1. 1.Dept. of ZoophysiologyUppsala UniversityUppsalaSweden
  2. 2.Dept. of PharmacologyPharmacia AB, Pharmaceuticals UppsalaUppsalaSweden
  3. 3.Dept. of Microbiology & ImmunologyUCLA School of MedicineLos AngelesUSA
  4. 4.Dept. of Food ScienceSwedish University of Agricultural SciencesUppsalaSweden

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