Gastroenterology

Gastroenterology

Volume 107, Issue 6, December 1994, Pages 1643-1652
Gastroenterology

Dextran sulfate sodium-induced colitis occurs in severe combined immunodeficient mice

https://doi.org/10.1016/0016-5085(94)90803-6Get rights and content

Abstract

Background/Aims: 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 interieukin (IL) 1β, 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.

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    Supported in part by a fellowship grant F05TWO 9270-02 (to L.A.D.) from the Fogarty Foundation, National Institutes of Health; a scholarship (to B.U.R.) from the Verenigde Spaar Bank, The Netherlands; and National Institutes of Health grant P01 DK44240.

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    Dr. Beagley's present address is: Department of Pathology, University of Newcastle, Newcastle, Australia.

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