Dextran sulphate sodium-induced colitis is ameliorated in interleukin 4 deficient mice.
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.
Stevceva
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Division of Molecular Medicine, John Curtin School of Medical Research, ANU, Canberra, ACT, 2601, Australia. stevcevl@mail.nih.gov
Pavli
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P
Husband
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Ramsay
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Doe
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D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000473:pathology; D016264:Dextran Sulfate / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D007136:Immunoglobulins / Q000097:blood; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D007136:Immunoglobulins; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D016264:Dextran Sulfate