Mechanisms of action of anti-TNF-α antibodies in inflammatory bowel disease and their clinical implications: an update

Mechanisms of action of anti-tumor necrosis factor alpha (anti-TNF-α) antibodies in therapy for inflammatory bowel disease are incompletely understood. Binding of antibodies to transmembrane TNF seems to be crucial for the induction of several cellular responses, including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity and reverse signaling. However significant, these processes alone do not fully explain the diversity of therapeutic responses seen in different patients. Thus, in this review we also explore some new and less frequently discussed aspects of anti-TNF-α blockade. In particular, a complex role of macrophages, T regulatory cells and intestinal endothelial cells is presented. We also discuss the clinical relevance of responses attributed to the Fc region of anti-TNF-α antibodies.