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 Printable version |
In vitro analysis of IGN-gamma and IL-12 production and their effects in ileal Crohn’s disease |
European Cytokine Network. Volume 13, Number 4, 431-7, December 2002, Articles originaux
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 Free Article
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Author(s) : Stefaan Colpaert, Kathleen Vastraelen, Zhanju Liu, Philippe Maerten,Chong Shen, Freddy Penninckx, Karel Geboes, Paul Rutgeerts, Jan L Ceuppens |
Summary : Crohn's disease is an inflammatory disease of the gut in which tumour necrosis factor (TNF) and T helper 1 (Th1) cytokines (interleukin (IL)-12, interferon (IFN)-g) are thought to play a major role. After the successes obtained with neutralisation of TNF, interest is now growing for therapy aiming at neutralisation of Th1-associated cytokines. Since cytokines are linked in a delicate network, in vitro cultures of ileal lamina propria mononuclear cells (LPMC) were set up for evaluation of a) IFN-g and IL-12 production, b) effects of rhIFN-g and rhIL-12 and c) effects of anti-IFN-g and anti-IL-12 on pro-inflammatory cytokines and IL-10 production. LPMC were isolated from surgical specimens of a total of 27 Crohn's disease and 17 caecum carcinoma (control) patients. Cells were stimulated with CD40L (which triggers myeloid CD40-expressing cells) or anti-CD3 +CD80 (which triggers T cells). LPMC from involved ileal, Crohn's disease produced, in both non-stimulated and stimulated conditions, more IFN-g and IL-12p70 than LPMC from non-involved tissue or from control patients. rhIFN-g significantly enhanced TNF production in both controls and in ileal Crohn's disease patients, while rhIL-12 enhanced IFN-g but not TNF production. LPMC from involved tissue were more sensitive to IL-12 than control LPMC. LP-T cell-dependent activation of monocytes was then studied by co-culture of anti-CD3/CD80-stimulated LPMC with fresh monocytes, which resulted in high IL-12, IFN-g, TNF and IL-10 production. The data show that neutralisation of either IL-12 or IFN-g with mAb in these cultures also affects secretion of the reciprocal cytokine and (in the case of anti-IL-12) also that of the anti-inflammatory cytokine IL-10. However, no effect of anti-IL-12 or anti-IFN-g on production of TNF, a cytokine with an important pathogenic role in Crohn's disease, could be found. Therapies aiming at neutralisation of IFN-g or IL-12 are therefore unlikely to replace anti-TNF, but they might provide an additive or synergistic effect. |
Keywords : IL-12; IFN-g; anti-IL-12/ anti-IFN-g; in vitro; Crohn's disease |
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