INTESTINAL INFLAMMATION - A COMPLEX INTERPLAY OF IMMUNE AND NONIMMUNECELL-INTERACTIONS

Intestinal inflammation has traditionally been viewed as a process in which effector immune cells cause the destruction of other mucosal cel ls that behave as passive bystander targets. Progress in understanding the process of intestinal inflammation has led to a much broader and more integrated picture of the various mucosal components, a picture i n which cytokines, growth factors, adhesion molecules, and the process of apoptosis act as functional mediators. Essentially all cellular an d acellular components can exert immunelike activities, modifying the classical concept of selected immune cells acting on all other cells t hat has been the dogma of immunologically mediated tissue damage for d ecades. The existence of specialized communication pathways between ep ithelial cells and T cells is well documented, including abnormal epit helial cell-mediated T cell activation during inflammation. Mesenchyma l cells contribute to fibrosis in the inflamed gut but are also respon sible for retention and survival of leukocytes in the mucosa. In chron ically inflamed intestine the local microvasculature displays leukocyt e hyperadhesiveness, a phenomenon that probably contributes to persist ence of inflammation. The extracellular matrix regulates the number, l ocation, and activation of leukocytes, while metalloproteinases regula te the quantity and type of deposited matrix proteins. This evidence f rom the intestinal system, consolidated with the use of data from othe r organs and systems, reveals a rich network of reciprocal and finely orchestrated interactions among immune, epithelial, endothelial, mesen chymal, and nerve cells and the extracellular matrix. Although these i nteractions occur under normal conditions, the dysfunction of any comp onent of this highly integrated mucosal system may lead to a disruptio n in communication and result in pathological inflammation.