Mode of function of biological anti-TNF agents in the treatment of inflammatory bowel diseases.
TNF-alpha 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-beta 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.
Tilg
Herbert
H
Medical University Innsbruck, Department of Medicine, Division of Gastroenterology and Hepatology, Innsbruck, Austria. herbert.tilg@i-med.ac.at
Moschen
Alexander
A
Kaser
Arthur
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D017209:Apoptosis / Q000187:drug effects; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000502:physiology; D000068582:Certolizumab Pegol; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D000069285:Infliximab; D009000:Monocytes / Q000187:drug effects; D011092:Polyethylene Glycols / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019013:CD40 Antigens; D007140:Immunoglobulin Fab Fragments; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D011092:Polyethylene Glycols; D000069285:Infliximab; D000068582:Certolizumab Pegol