Intestinal Epithelial Cells as a Source of Inflammatory Cytokines and Chemokines

The intestinal epithelium has long been known to provide nonspecific defences such as mucus, lysozyme and transport of secretory immunoglobulin via the polyimmunoglobulin receptor. In the past decade, the realization emerged that enterocytes secrete molecules (cytokines) that regulate inflammation. As the focus tightened on this new role as sentinel, so has the interest in enterocyte production of cytokines with chemoattractant properties for leukocytes - the chemokines. Neutrophils are a prominent feature of the cellular infiltrate in various inflammatory diseases, and early reports indicated that epithelial cells secrete neutrophil chemoattractants. More recently, it has been shown that the cells also secrete chemokines for monocytes and lymphocytes. Some of these chemokines appear to be important in the uninflamed intestine but become increased during disease. While a great deal of knowledge has been gained regarding the circumstances leading to chemokine production by epithelial cells, the application of this understanding to the treatment of human intestinal diseases is lacking. Closing this gap is necessary to take advantage of emerging therapies aimed at blocking chemokine function.