Intestinal epithelial hyperpermeability: update on the pathogenesis of gut mucosal barrier dysfunction in critical illness.
OBJECTIVE
Tight junctions between adjacent epithelial cells are essential for the maintenance of compositionally distinct fluid compartments in various organs, such as the liver, lungs, kidneys, and intestine. These epithelial organs are commonly affected in the condition known as multiple organ dysfunction syndrome, which can complicate the clinical course of patients with sepsis or other conditions associated with poorly controlled systemic inflammation. The gut serves as a useful model for this problem, and studies using reductionist in vitro models and experiments carried out using laboratory animals are starting to clarify the cellular and biochemical mechanisms that are responsible for intestinal epithelial hyperpermeability secondary to critical illness.


RESULTS
One key factor that has been identified is excessive production of nitric oxide and related species, although other factors, such as increased expression of the cytokine interleukin 6, appear to be important as well. A newly described, cytokine-like molecule, high-mobility group B1, increases permeability of cultured epithelial monolayers in vitro and murine ileal mucosa in vivo.


CONCLUSIONS
Epithelial dysfunction may be a common final pathway contributing to organ dysfunction in sepsis and other forms of critical illness.
Fink
Mitchell P
MP
Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15260, USA. finkmp@ccm.upmc.edu
D000818:Animals; D002460:Cell Line; D016638:Critical Illness; D016207:Cytokines / Q000096:biosynthesis; D004848:Epithelium / Q000503:physiopathology; D005767:Gastrointestinal Diseases / Q000503:physiopathology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000503:physiopathology*; D007421:Intestine, Small / Q000503:physiopathology*; D009102:Multiple Organ Failure / Q000209:etiology; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress; D010539:Permeability; D017382:Reactive Oxygen Species / Q000378:metabolism
D016207:Cytokines; D017382:Reactive Oxygen Species; D009569:Nitric Oxide