Journal
EXPERT OPINION ON THERAPEUTIC TARGETS
Volume 8, Issue 4, Pages 287-294Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/14728222.8.4.287
Keywords
adhesion molecule; apoptosis; Crohn's discase (CD); gp130,IL-6; monoclonal antibody (mAb); pro-inflammatory cytokine; soluble IL-6 receptor (sIL-6R); therapy
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The aetiology of Crohn's disease (CD) remains unknown, however, the importance of pro-inflammatory cytokines including IL-6 has been shown. IL-6 can transduce its signal into the cells lacking membrane-bound receptors by forming a complex with soluble IL-6R (sIL-6R). To pursue the therapeutic potential of IL-6 signalling blockade for CD, anti-IL-6R monoclonal antibody (mAb) was introduced to experimental colitis, and successfully prevented and treated intestinal inflammation by suppressing vascular adhesion molecules and by inducing lamina propria T cell apoptosis. Based on these results, the clinical trial of humanised anti-IL-6R mAb, MRA, was carried out. Eighty per cent of the patients given twice-weekly MRA had a significantly better clinical response rate as compared to 31% of the placebo-treated patients. The response rate of the every-4-weeks regimen was 42%. The incidence of adverse events was similar in all groups. These data strongly suggest a therapeutic potential of MRA for CD.
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