Abstract: | The intestinal epithelium plays an important role in the recognition of pathogenic organisms and in the recruitment of inflammatory cells to the mucosa. Epithelial chemokine production may constitute a key target in future therapies for inflammatory bowel disease (IBD). Chemokines are divided into two subfamilies, the C-C family and C-X-C family. Most C-C chemokines target mononuclear cells and many C-X-C chemokines attract neutrophils. Interleukin-8 (IL-8), a C-X-C chemokine, acts as a motor for the recruitment of neutrophils into the non-inflamed mucosa and is present in both enterocytes and mucosal inflammatory cells. Epithelial cells may be the first to signal the presence of pathogens, as well as contributing to IL-8 production in IBD. Data have also shown that intestinal epithelial cells are able to respond to IL-1β and tumour necrosis factor-alpha (TNF-α) at concentrations known to occur in the inflamed mucosa. Monocyte chemotactic protein-1 (MCP-1), a member of the C-C chemokine family, is noticeably increased in IBD. These data show that C-X-C and C-C chemokines are equally important properties of mucosal epithelial cells. The effects of two anti-inflammatory drugs (dexamethasone and cyclosporin) on chemokine production are significantly different and this provides a rationale for combination therapy. |