Dextran sulphate sodium-induced colitis is ameliorated in interleukin 4 deficient mice

Abstract

The importance of IL-4 and its effects in inflammatory bowel disease (IBD) was studied using the dextran sulphate sodium-induced model of experimental colitis. The model resembles ulcerative colitis in humans. IL-4 deficient mice and IL-4+/+ littermates were used to induce colitis. Activity of disease, extent of tissue damage, immunoglobulin isotypes, IFNgamma and IL-10 production was assessed. Both disease activity index (DAI) and histological scores were consistently lower in the IL-4 deficient mice than in the IL-4+/+ littermates. Furthermore, the lower histological scores reflected the milder inflammatory lesions and decreased ulceration found in the IL-4 deficient mice. Analysis of immunoglobulin subtypes showed that IgG1 was almost absent in the sera of IL-4 deficient mice. IFNgamma contents was much higher in colonic tissues from IL-4 deficient mice. Dextran sulphate sodium-induced colitis is ameliorated in IL-4 deficient mice. IL-4 either directly or through its effects on T and B cells influences its severity. It is unclear if the higher immunoglobulin-producing cells in the colonic tissues of IL-4 deficient mice before colitis was induced could have influenced the outcome of the disease. The high IFNgamma contents in colonic tissues of IL-4 deficient mice argue against the role of this cytokine as a crucial mediator of tissue damage during the acute phase of colitis.

Proinflammatory properties of IL-4 in the intestinal microenvironment

“…Colitis induced by IL-4 overexpression was evident in CD4 and RAG-2-deficient mice, indicating a T cell-independent mechanism. This is supported by a previous study (23) in which colitis induced by DSS, which is generally accepted to be a T cell-independent model, was ameliorated in IL-4-deficient mice. The ability of IL-4 to exacerbate a Th-1-driven model of colitis suggests that IL-4 may also exert proinflammatory effects in a context of T cell-mediated injury (11).…”

IL-1 receptor-associated kinase M downregulates DSS-induced colitis†

“…41 Th2 cytokines such as IL-4 and IL-5 are upregulated in the mucosa from UC patients and, interestingly, DSS-induced colitis is ameliorated in IL-4-deficient mice, 42,43 indicating that IL-4 is important for colonic homeostasis. Patients with IBD have elevated levels of FoxP3 in the colonic mucosa.…”

Nod1 Limits Colitis-Associated Tumorigenesis by Regulating IFN-γ Production

“…In a model of colitis-associated tumorigenesis that utilizes AOM together with trinitrobenzene sulfonic acid (TNBS),which induces colitis, IL-4 was suggested to promote tumorigenesis while IFNγ was protective. In addition, IL-4 has also been implicated in exacerbating colitis and tumor growth in mice (27, 32). IL-4 can also inhibit IFNγ production.…”