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Title: Involvement of interleukin 18 in Crohn's disease: evidence from in vitro analysis of human gut inflammatory cells and from experimental colitis models
Authors: Maerten, Philippe
Shen, Chong
Colpaert, S
Liu, Zhe
Bullens, Dominique
Van Assche, Gert
Penninckx, Freddy
Geboes, Karel
Vanham, G
Rutgeerts, Paul
Ceuppens, Jan #
Issue Date: Jan-2004
Series Title: Clinical and Experimental Immunology vol:135 issue:2 pages:310-7
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.
URI: 
ISSN: 0009-9104
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Research in GastroIntestinal Disorders
Laboratory for Clinical Infectious and Inflammatory Disorders
Abdominal Surgical Oncology
Translational Cell & Tissue Research
Laboratory of Clinical Immunology
Laboratory of Pediatric Immunology
# (joint) last author

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