Infliximab, a Drug for Crohn's Disease

TNF-α originates as a membrane-anchored precursor (pro-TNF) which is cleaved by the metalloproteinase TNF-α-converting enzyme (TACE), to then be secreted as a 17-kDa soluble protein. TNF-α exerts its effects through binding either one of the TNF-α receptors (TNFRs), TNFR1 or TNFR2.Infliximab(IFX) is a chimeric monoclonal Ig G1 (75% human and 25% murine) anti-TNF-α. IFX is able to bind soluble and membrane-bound TNF, and in vitro data suggest that it can induce T-cell apoptosis via complement activation or antibody-dependent cell cytotoxicity.Besides its action on immune and epithelial cells, TNF-α plays a crucial role in regulating cell adhesion molecule expression by intestinal endothelium and fibroblasts. Crohn's Disease (CD) patients undergoing IFX treatment down-regulate the expression levels of the vascular cell adhesion molecule (VCAM-1) and CD40 on the intestinal mucosal endothelium, thus inhibiting T-cell recruitment. In addition to TNF-α blockade and apoptosis induction, IFX exerts a wide spectrum of anti-inflammatory activities. For instance, IFX reduces the circulating levels of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). These two cytokines, proposed as markers of fibrosis and angiogenesis, are typically over-expressed in CD.