Dextran sulfate sodium-induced colitis occurs in severe combined immunodeficient mice.
OBJECTIVE
Oral administration of dextran sulfate sodium (DSS) has been reported to induce colitis in mice. The purpose of this study was to determine whether the possible pathogenic mechanism involved the acquired immune system.


METHODS
Normal BALB/c and related C.B17 severe combined immunodeficient mice were fed 5% DSS (40 kilodaltons) in their drinking water for 7 days; controls were fed only water. Colons were scored for histological activity at various times. Cytokine production by cultures of colon and of draining lymph node cell was measured. The effect of DSS on the proliferation of the MCA-38 colonic epithelial cell line was assessed.


RESULTS
DSS feeding resulted in a very reproducible acute distal colitis in both BALB/c and C.B17 severe combined immunodeficient mice. The lesions of BALB/c mice had an increased production of macrophage-derived cytokines, such as interleukin (IL) 1 beta, IL-6, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor, but not the T-cell cytokines IL-3 or interferon gamma. Draining lymph node cells produced these cytokines plus interferon gamma and IL-3. DSS inhibited MCA-38 cells at doses that would be easily achieved in the distal colon.


CONCLUSIONS
Acute DSS-induced colitis does not require the presence of T cells or B cells because it occurred in C.B17 severe combined immunodeficient mice that lack these cells. Its induction may result from a toxicity of DSS for colonic epithelial cells.
Division of Gastroenterology, Free University of Amsterdam, The Netherlands.
L A
LA
Dieleman
B U
BU
Ridwan
G S
GS
Tennyson
K W
KW
Beagley
R P
RP
Bucy
C O
CO
Elson
D000208:Acute Disease; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016264:Dextran Sulfate / Q000009:adverse effects*; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D007377:Interleukin-3 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D007377:Interleukin-3; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016264:Dextran Sulfate