One of the more recent clinical advances in inflammatory bowel disease (IBD) therapy has been due to the recognition of the role of adhesion molecules in inflammation. These molecules regulate the “sticking” of inflammatory cells to a number of tissues and produce disease. The earliest work in this field, from the 1970s, studied how these molecules could regulate organ-specific metastasis by cancer cells. With the identification of adhesion molecules, their role was also sought in a number of inflammatory diseases. To date, adhesion molecules have been studied in a wide range of diseases and target organs.

Over a decade ago we identified differences in adhesion molecule expression in peripheral blood and isolated gut lamina propria lymphocytes from patients with ulcerative colitis (UC), Crohn’s disease (CD), and “normals.” 1 We studied adhesion molecules of the VLA integrin family. Integrin adhesion molecules consist of several “pairs” of adhesion molecules and complementary “addressins” or target addresses. These include CD11a/CD18-LFA-1 (alphaLBeta2), which is expressed on all leukocytes. It binds to ICAM-1 and ICAM-2, and VLA-4. It is expressed on lymphocytes, eosinophils, and monocytes and binds to VCAM-1 and extracellular matrix molecules. CD49d/Beta7–(alpha4Beta7) is expressed on lymphocytes and binds to the mucosal addressin MAdCAM and VCAM-1 fibronectin. The mucosal addressin molecule MAdCAM is involved with mucosal specific homing of lymphocytes to the gut. We also studied the expression of these molecules in an animal model of inflammation, the HLA-B27 transgenic rat model of IBD. Similar mechanisms of cell trafficking and homing exists in this animal model compared to human IBD. The first clinical use of a specific antiadhesion therapy used antisense technology. Although there have been negative outcomes to several clinical trials of systemically administered antisense to ICAM-1, more recent studies using antisense as topical, enema therapy has shown positive clinical response with durability. Most biologic drugs currently used are based on monoclonal antibody technology. Antisense technology has proven tricky to develop; however, it can provide significant advantages as a drug platform compared to antibody technology. First, the antisense acts at a transcriptional level, and therefore acts to prevent adhesion molecule