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World J Gastroenterol. Nov 28, 2010; 16(44): 5523-5535
Published online Nov 28, 2010. doi: 10.3748/wjg.v16.i44.5523
Interplay between inflammation, immune system and neuronal pathways: Effect on gastrointestinal motility
Benedicte Y De Winter, Joris G De Man
Benedicte Y De Winter, Joris G De Man, Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, 2610 Antwerp, Belgium
Author contributions: De Winter BY reviewed the literature, designed and wrote the manuscript; De Man JG revised the manuscript critically and approved the final version.
Correspondence to: Benedicte Y De Winter, MD, PhD, Executive Director, Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium. benedicte.dewinter@ua.ac.be
Telephone: +32-3-2652710 Fax: +32-3-2652567
Received: July 12, 2010
Revised: July 30, 2010
Accepted: August 6, 2010
Published online: November 28, 2010

Sepsis is a systemic inflammatory response representing the leading cause of death in critically ill patients, mostly due to multiple organ failure. The gastrointestinal tract plays a pivotal role in the pathogenesis of sepsis-induced multiple organ failure through intestinal barrier dysfunction, bacterial translocation and ileus. In this review we address the role of the gastrointestinal tract, the mediators, cell types and transduction pathways involved, based on experimental data obtained from models of inflammation-induced ileus and (preliminary) clinical data. The complex interplay within the gastrointestinal wall between mast cells, residential macrophages and glial cells on the one hand, and neurons and smooth muscle cells on the other hand, involves intracellular signaling pathways, Toll-like receptors and a plethora of neuroactive substances such as nitric oxide, prostaglandins, cytokines, chemokines, growth factors, tryptases and hormones. Multidirectional signaling between the different components in the gastrointestinal wall, the spinal cord and central nervous system impacts inflammation and its consequences. We propose that novel therapeutic strategies should target inflammation on the one hand and gastrointestinal motility, gastrointestinal sensitivity and even pain signaling on the other hand, for instance by impeding afferent neuronal signaling, by activation of the vagal anti-inflammatory pathway or by the use of pharmacological agents such as ghrelin and ghrelin agonists or drugs interfering with the endocannabinoid system.

Keywords: Sepsis, Ileus, Nitric oxide, Prostaglandins, Oxidative stress, Residential macrophages, Mast cells, Neurons, Afferent, Neuroimmunomodulation, Inflammation