Mentation on the immunological modulation of gastrointestinal motility

The immunological modulation of gastrointestinal motility is currently one of the most dynamic and fascinating areas of enteric research, as investigators are beginning to focus their studies on the pathophysiology of various gastrointestinal dysmotilities. The new fruits of this investigative initiative has resulted in the appearance of a fascinating series of articles which demonstrate that intestinal inflammatory events alter a distinct population of enteric neurons and that these alterations last long past the apparent resolution of the inciting event. Studies over the past few years have unequivocally demonstrated that the muscularis externa itself is an active and complex immunological compartment with unique features. The rodent muscularis externa is constitutively populated by a dense network of muscularis macrophages throughout the entire gastrointestinal tract. Although few other leukocytes are present in the rodent, the human muscularis is densely populated by both macrophages and mast cells. Postoperative ileus and endotoxin-induced ileus have turned out to be extremely useful rodent models to elucidate the importance of muscularis leukocytes in causing intestinal dysfunction. Using models of ileus, studies have demonstrated that a complex molecular inflammatory scenario is triggered within the muscularis externa, which consists of MAP kinase phosphorylation, transcriptior factor activation and the subsequent induction of various cytokines, chemokines and, importantly, smooth muscle inhibitory substances, such as nitric oxide and prostaglandins from iNOS and COX-2. This local molecular inflammatory milieu leads to leukocyte extravasation. Data suggests that the muscularis macrophage network is the conductor of the molecular and cellular inflammatory responses which causes ileus.