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 thymus-derived 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.

Background: Animal models of inflammatory bowel disease are artificial and more or less representative of human disease. However, the dextran sulphate sodium (DSS) induced intestinal inflammation model has recently been shown to fulfil some pathological criteria for an adequate experimental model. Aim: To determine whether this form of experimental intestinal inflammation responds to established therapy used for human inflammatory bowel disease. Methods: DSS was used to induce intestinal inflammation in conventional Balb/c mice and athymic nu/nu CD‐1(BR) mice, and the well‐documented 5‐aminosalicylic acid (5‐ASA) based anticolitis drugs sulphasalazine (SASP) and olsalazine (OLZ) were used to study therapeutic effects. Parameters which have been shown to reflect DSS‐induced intestinal inflammation (body weight, colon length, spleen weight, diarrhoea, and rectal bleeding) were measured in the Balb/c mice. Results: Significant amelioration was seen on these parameters after different treatment protocols. Survival in nu/nu CD‐1 mice was studied, and after 16 days a death rate of 50% was noted in the DSS group. SASP (100 mg/kg/day) and OLZ (50 mg/kg/day) significantly prolonged the survival to 29 and 38 days, respectively. SASP and OLZ showed a dose‐dependent effect in the range between 10 and 100 mg/kg/day, doses closely corresponding to those used in humans. Conclusions: SASP and OLZ are able to ameliorate the DSS‐induced intestinal inflammation. The dose‐response patterns suggested that the active therapeutic moiety for the two drugs appears to be mainly the liberated 5‐ASA molecule.

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There is a need for better understanding of the roles of dietary fats and fibers in colon cancer risk. We examined the effect of different dietary fiber and fat sources on an azoxymethane (AOM)-induced colon cancer in rats. In a 2 x 3 factorial design, rats were fed a semipurified diet containing soy-derived fiber (Fibrim), alpha-cellulose (Solkafloc) or resistant starch (RS; Hi-maize) at 10 g dietary fiber/100 g diet, combined with fish oil (FO) or sunflower seed oil (SSO) at 10 g/100 g diet, and lard added to all diets at 10 g/100 g, to provide a total of 20 g mixed fat/100 g diet. Sprague-Dawley rats (28 d of age) consumed diets for 4 wk and then two doses of AOM (15 mg/kg body) were administered 1 wk apart by subcutaneous injection. Rats were killed after 13 wk of consuming experimental diets. Colons were fixed in formalin and aberrant crypt foci (ACF) were quantified after staining. ACF counts were higher (+66%, P < 0.01) in rats fed SSO and RS, than in those fed alpha-cellulose and FO. Rats fed FO had 19% fewer ACF than those fed SSO (P < 0.05). alpha-Cellulose was associated with the highest cecal butyrate concentration (P < 0.001), the highest beta-glucuronidase specific activity (P < 0.001) and the lowest cecal water cytotoxicity (P < 0.001) relative to soy fiber- and RS-fed rats. There were inverse correlations between the number of ACF and cecal butyrate concentration (r = -0.33, P < 0.05) and between cecal water cytotoxicity and beta-glucuronidase activity (r = -0.70, P < 0.001). The greatest protection was associated with alpha-cellulose as the fiber source and FO as the fat source as measured by colon ACF numbers in rats.