Altered permeability in inflammatory bowel disease: pathophysiology and clinical implications.
OBJECTIVE
To present the mechanisms behind barrier disturbance in inflammatory bowel disease and their functional consequences.


RESULTS
A reduction in tight junction strands, strand breaks and alteration of tight junction protein content and composition characterize Crohn's disease. In ulcerative colitis, epithelial leaks appear early as a result of microerosions, upregulated epithelial apoptosis and tight junction protein changes with pronounced increases in claudin-2. T-helper type 1 cytokine effects by interferon-gamma and tumour necrosis factor alpha are important for epithelial damage in Crohn's disease. Interleukin-13 is the key effector cytokine in ulcerative colitis, stimulating epithelial cell apoptosis, and can upregulate claudin-2 expression. Together with interleukin-13-induced epithelial restitution arrest, this may explain why ulcer lesions occur in early stages of ulcerative colitis but are only observed in advanced inflammatory stages in Crohn's disease.


CONCLUSIONS
Barrier dysfunction in inflammatory bowel disease contributes to diarrhea by a leak flux mechanism and can cause mucosal inflammation secondary to luminal antigen uptake. Barrier abnormalities, such as epithelial tight junction changes and apoptotic leaks, gross mucosal lesions, and epithelial restitution arrest are responsible for these abnormalities and are the result of immune dysregulation. Studying the underlying mechanisms is important in understanding the pathophysiology of inflammatory bowel disease and developing therapeutic strategies.
Mankertz
Joachim
J
Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité - Campus Benjamin Franklin, Berlin, Germany.
Schulzke
Jörg-Dieter
JD
D017209:Apoptosis; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000503:physiopathology*; D007371:Interferon-gamma / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology; D008565:Membrane Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma