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Involvement of interleukin 18 in Crohn's disease: evidence from in vitro analysis of human gut inflammatory cells and from experimental colitis models

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Show simple item record Maerten, P. en_US Shen, C. en_US Colpaert, S. en_US Liu, Z. en_US Bullens, D. A. M. en_US Van Assche, G. en_US Penninckx, F. en_US Geboes, K. en_US Vanham, G. en_US Rutgeerts, P. en_US Ceuppens, J. L. en_US 2007-12-06T14:47:30Z 2007-12-06T14:47:30Z 2004 en_US
dc.identifier.issn 0009-9104 en_US
dc.identifier.other ITG-M9A en_US
dc.identifier.other MICRO en_US
dc.identifier.other U-IMMUN en_US
dc.identifier.other JIF en_US
dc.identifier.other DOI en_US
dc.identifier.other ABSTRACT en_US
dc.description.abstract An imbalance of immunoregulatory factors and/or cells contributes to uncontrolled mucosal T cell activation and inflammation in Crohn's disease (CD). Bioactive interleukin (IL)-18 has been shown to be produced by macrophages in CD lesions. We report here that T cells freshly isolated from inflamed tissue of CD patients (and not T cells from control intestinal tissue) were responsive to IL-18. In the presence of IL-18, these T cells produced more interferon (IFN)-gamma and less IL-10. To analyse further the role of IL-18 in this disease, an acute and a chronic model of murine colitis were used. IL-18 mRNA was significantly enhanced in trinitrobenzene sulphonic acid (TNBS) induced colitis, and treatment with IL-18 binding protein (IL-18BPa), which neutralizes IL-18 bioactivity, significantly reduced the severity of colitis. However, IL-18BPa did not affect the course of chronic colitis in CD45RBhighCD4+ T cell reconstituted SCID mice. Production of IFN-gamma in lamina propria mononuclear cell cultures from IL-18BPa-treated SCID mice was decreased, but at the same time fewer lamina propria CD4+ T cells harvested from IL-18BPa-treated mice compared to non-treated mice were in apoptosis. We conclude that IL-18 clearly has a modulatory role in the inflammatory cascade of CD and experimental colitis by affecting IFN-gamma and IL-10 production, and apoptosis. In view of the divergent effects of IL-18 neutralization in the two different murine colitis models, it is unlikely that IL-18 is at the top of this cascade. en_US
dc.language English en_US
dc.subject Infectious diseases en_US
dc.subject Crohn disease en_US
dc.subject Colitis en_US
dc.subject Apoptosis en_US
dc.subject T-cells en_US
dc.subject Interleukin-18 en_US
dc.subject IL-18 en_US
dc.subject Interleukin-10 en_US
dc.subject IL-10 en_US
dc.subject Interferon-gamma en_US
dc.subject IFN-g en_US
dc.title Involvement of interleukin 18 in Crohn's disease: evidence from in vitro analysis of human gut inflammatory cells and from experimental colitis models en_US
dc.type Article en_US
dc.citation.issue 2 en_US
dc.citation.jtitle Clinical and Experimental Immunology en_US
dc.citation.volume 135 en_US
dc.citation.pages 310-317 en_US
dc.citation.jabbreviation Clin Exp Immunol en_US

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