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 Printable version |
Effects of murine recombinant interleukin-10 on the inflammatory disease of rats transgenic for HLA-B27 and human 2-microglobulin |
European Cytokine Network. Volume 9, Number 2, 161-70, June 1998, Articles originaux
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 Free Article
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Author(s) : V. Bertrand, S. Quéré, R. Guimbaud, P. Sogni, L. Chauvelot-Moachon, M. Tulliez, D. Lamarque, J. Charreire, J.P. Giroud, D. Couturier, S. Chaussade, M. Breban |
Summary : Rats transgenic for HLA-B27 and human beta 2-microglobulin develop a spontaneous, multisystem, inflammatory disease that resembles human B27-associated disease and that involves the gut mucosa. This model predominantly affects the colon and is characterized by an extensive infiltration of the mucosa by inflammatory cells, largely composed of mononuclear cells. In addition, an increased plasma level of nitric oxide (NO)-derived metabolites was described in this model. Deficiency in the anti-inflammatory cytokine, interleukin-10 (IL-10), leads to the development of colitis in IL-10 knockout mice, suggesting that IL-10 plays a major role in the control of gut inflammation. The objectives of this work were to study the mechanisms of the inflammatory bowel disease (IBD) in HLA-B27 rats and to determine the effects of treatment with IL-10. The 33-3 line of HLA-B27 recombinant rats with established disease was treated in two consecutive experiments with murine recombinant IL-10 for five weeks. Assessment of the effect of this treatment was performed, based on clinical, histological and biological (myeloperoxidase and inducible NO synthase activities; tumor necrosis factor- , interferon- , CD3, iNOS and -actin mRNA expression. In 33-3 rats with established disease, mesenteric lymph nodes were hyperplastic, and colonic cellularity and MPO and iNOS activities in the colonic mucosa were increased without any detectable effects of IL-10 administration. IFN- and iNOS mRNA were only detected in the colon of transgenic rats. Despite a lack of effect on disease expression, IL-10 strikingly reduced the level of IFN- mRNA in gut mucosa. Up-regulation of IFN- mRNA suggests that the IBD of HLA-B27 rats is mediated by T-helper 1 lymphocytes. Sustained administration of IL-10, in HLA-B27 rats with established disease, efficiently inhibited IFN- mRNA expression but did not influence disease expression: these results indicate that IFN- may exert a critical role at an earlier stage of the disease rather in the maintenance of the lesions. |
Keywords : HLA-B27transgenic rats, interferon- , IL-10, inducible NO synthase, inflammatory bowel disease. |
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