Novel approaches to treating inflammatory bowel disease: Targeting alpha-4 integrin

Crohn's disease involves persistent recruitment of leukocytes into gut tissue, coupled with dysregulated activation of specific immune cell function. Adhesion molecules expressed by circulating leukocytes, such as alpha4 integrin, mediate their attachment to vascular endothelial cells lining blood vessels within the intestine and facilitate their migration into the tissue. Through interactions with extracellular matrix molecules, adhesion molecules then support immune cell activation and survival within the intestinal wall. Agents that interfere with these adhesive interactions hold great potential for suppressing the cycle of leukocyte infiltration and activation, and thereby, for ameliorating chronic inflammation. This article will discuss clinical data for a humanized monoclonal antibody against alpha4 integrin, natalizumab, which is the first alpha4 integrin antagonist in a new class of biotechnology agents referred to as selective adhesion molecule inhibitors. (C) 2003 by Am. Coll. of Gastroenterology.