Focus on mechanisms of inflammation in inflammatory bowel disease sites of inhibition: current and future therapies.
Anti-TNF antibodies were the first biologic agents registered to treat patients who have CD and, more recently, patients who have UC. The sequence of events underlying the inflammatory reaction in IBD is extremely complex, however, and involves both the innate and antigen-driven adaptive immune system. Novel therapies are directed at several key players of this cascade. Blockade of T-cell proliferation and activation and inhibition of T-cell cytokines has been most extensively targeted by clinical trials in humans. Inhibition of adhesion molecules and the use of selected growth factors seem to have therapeutic potential. Restoration of regulatory T-cell and dendritic-cell function is still waiting to be explored in clinical trials. Although an increasing number of biologic therapies for IBD are being developed, the discovery of the full spectrum of treatment modalities is only beginning. Often, however, the clinical efficacy of biologic agents is investigated, and for some molecules is established, before mechanisms of action are specifically explored. Eight years after the Food and Drug Administration approved infliximab for the treatment of luminal CD, it is not known how this anti-TNF antibody actually dampens inflammation in IBD. The advent of newer anti-TNF agents is only postponing the answer.
Van Assche
Gert
G
Division of Gastroenterology, University of Leuven Hospitals, Herestraat 49, B-3000 Leuven, Belgium.
Vermeire
Séverine
S
Rutgeerts
Paul
P
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015703:Antigens, CD / Q000187:drug effects / Q000276:immunology; D001323:Autoantibodies / Q000627:therapeutic use; D001691:Biological Therapy / Q000639:trends; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors; D016207:Cytokines / Q000037:antagonists & inhibitors*; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D001323:Autoantibodies; D015815:Cell Adhesion Molecules; D016207:Cytokines; D005765:Gastrointestinal Agents; D018121:Receptors, Cytokine