Mode of function of biological anti-TNF agents in the treatment of inflammatory bowel diseases

Abstract

TNF-α has been identified as a major mediator in the pathophysiology of inflammation. Anti-TNF agents, either as a neutralising antibody or a soluble TNF receptor, have markedly influenced the clinical management of several chronic inflammatory disorders. Whereas it seems likely that neutralisation of soluble and membrane-bound TNF might be a key mechanism of any anti-TNF agent, the potential of the anti-TNF antibody infliximab to induce lymphocyte/monocyte apoptosis in Crohn's disease has been considered an additional important mechanism. Other potential mode of actions include induction of the anti-inflammatory cytokines IL-10 or TGF-β via retrograde signalling or induction of a certain subset of regulatory T cells. Certolizumab, a pegylated fully human anti-TNF monoclonal antibody also effective in Crohn's disease, lacks the capacity to induce apoptosis. Therefore, the capacity to induce apoptosis and neutralisation of TNF alone are insufficient to explain clinical efficacy of anti-TNF agents in human inflammatory bowel diseases.

Keywords::

• adalimumab
• certolizumab
• crohn's disease
• infliximab
• TNF-α
• ulcerative colitis