title: Interplay between inflammation, immune system and neuronal pathways: effect on gastrointestinal motility.
abstract: 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.
authors.forename: Benedicte-Y
authors.initials: BY
authors.lastname: De Winter
authors.forename: Joris-G
authors.initials: JG
authors.lastname: De Man
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017615:Enteric Nervous System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D005768:Gastrointestinal Hormones / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000294:innervation*; D006801:Humans; D045823:Ileus / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000378:metabolism; D009102:Multiple Organ Failure / Q000276:immunology / Q000503:physiopathology; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D005768:Gastrointestinal Hormones; D018836:Inflammation Mediators