Immune System Control of Intestinal Ion Transport

The immune system takes part in the regulation of intestinal water and electrolyte transport through the release of inflammatory mediators that act both directly and via the enteric nervous system to inhibit NaCl absorption and stimulate electrogenic Cl^- secretion. It is likely that immune system activation is a normal physiologic event. The intestinal tract is filled with antigens and, although the barrier function of the epithelium usually serves to prevent their transmigration into the lamina propria, it probable that, on occasion, antigen presentation does occur. Under these instances, the phagocytes may instantly respond by initiating an intestinal secretory response that washes these antigens away. Similarly, previous sensitization to dietary antigens may allow mast cell degranulation to initiate a cleansing secretory response. Certainly under pathological conditions such as infection with parasites, bacteria, and viruses, the immune-mediated intestinal secretory response can either wash away these offending microorganisms or, by exfoliating infected or colonized cells and initiating muscle contraction, may actually physically expulse them from the gastrointestinal tract. In chronic idiopathic inflammatory bowel diseases such as ulcerative colitis and Crohn's disease, this inflammatory response seems to be uncontrolled; thus, what is normally a protective mechanism promulgates disease. Many issues remain to be clarified concerning intestinal inflammation and the responses of target cells such as the epithelium, the vasculature, and the smooth muscle. For example, recent studies showing that Pavlovian conditioning can degranulate mast cells (108) suggests the involvement of the immune system in stress-related or behavioral/functional diarrheas. The next decade will clarify both the normal, pathological, and central nervous system-mediated intestinal secretory responses to immune system activation. Such studies will further our understanding of both normal and pathologic control of intestinal water and electrolyte transport.