Review article: the expanding role of biological agents in the treatment of inflammatory bowel disease - focus on selective adhesion molecule inhibition.
Inflammatory bowel disease presents in various forms. Its increasing incidence indicates that modern lifestyle triggers disease in genetically susceptible individuals. We present a model for inflammatory bowel disease pathophysiology and review the new biological therapies available. These biological agents have been developed to antagonise the processes of pathogenic inflammation, such as the reduction in T-lymphocyte apoptosis, increase in T-lymphocyte proliferation and increase in T-lymphocyte trafficking into the intestinal mucosa. Inhibitors of various inflammatory cytokines, including some antagonists to tumour necrosis factor, are effective therapies for inflammatory bowel disease. However, this class is associated with the risk of rare, but serious, side-effects, such as opportunistic infections and demyelinating diseases. The administration of anti-inflammatory cytokines, including interleukin-10 and interleukin-11, may theoretically be effective in reducing inflammation, although the clinical development of some of these therapies has been terminated. The selective inhibition of the adhesion molecules involved in T-lymphocyte trafficking can be effective in reducing gut inflammation. Of the selective adhesion molecule inhibitors under investigation, natalizumab has demonstrated efficacy in inflammatory bowel disease. The future of biological therapy for inflammatory bowel disease shows promise.
Rutgeerts
P
P
Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium. paul.rutgeerts@med.kuleuven.ac.be
Van Deventer
S
S
Schreiber
S
S
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D001688:Biological Products / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors; D016207:Cytokines / Q000502:physiology; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000628:therapy*; D000069285:Infliximab; D011956:Receptors, Cell Surface / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D001688:Biological Products; D015815:Cell Adhesion Molecules; D016207:Cytokines; D005765:Gastrointestinal Agents; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab