While the causes of IBD are unknown, several hypotheses have been suggested by studies.
More than 100 potential susceptibility genes identified.1
Genes involved in the ability to recognize bacteria (eg, NOD2) and autophagy (eg, ATG16L1).1
Foreign substances (antigens) may be the direct cause of inflammation.2
Bacteria may stimulate the immune system to produce inflammation.2
CHRONIC AND ABERRANT INFLAMMATION
Once the inflammation is triggered, the IBD patient’s immune system has difficulty “turning off” the immune response.2
Defects in normal gut immunity may contribute to the pathophysiology of IBD.3
A hallmark characteristic of IBD is an accumulation of excess infiltrating lymphocytes in the mucosa.4
- Antigen presentation can result in the activation of immune cells such as T cells and macrophages, and consequently, the release of proinflammatory cytokines (eg, TNF-α, interleukins)5
- The upregulation of these cytokines, including chemokines, results in the sustained and massive influx of lymphocytes5
- This migration is also facilitated, in part, by an increase in the expression of adhesion molecules that capture lymphocytes on the vascular endothelium of mucosal blood vessels6
Vermeire S, Van Assche G, Rutgeerts P. Inflammatory bowel disease and colitis: new concepts from the bench and the clinic. Curr Opin Gastroenterol. 2011;27(1):32-37.
Crohn’s and Colitis Foundation of America. About Crohn’s disease. 2009.http://www.ccfa.org/info/about/crohns. Accessed March 28, 2012.
Hanauer S. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities.Inflamm Bowel Dis. 2006;12(Suppl 1):S3-S9.
Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448(7152):427-434.
Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007;369(9573):1627-1640.
Koizumi M, King N, Lobb R, Benjamin C, Podolsky DK. Expression of vascular adhesion molecules in inflammatory bowel disease. Gastroenterology. 1992;103(3):840-847.
Stedman’s Medical Dictionary. 27th ed. New York, NY: Lippincott Williams & Wilkins; 2000.
Janeway CA Jr, Travers P, Walport M, Shlomchik MJ. Immunobiology: The Immune System in Health and Disease. 6th ed. New York, NY: Garland Science Publishing; 2005.
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Autophagy: segregation and disposal of damaged organelles within a cell7
Antigen: any molecule that can bind specifically to an antibody8
Lymphocytes: a class of white blood cells that bear variable cell-surface receptors for antigen; there are 2 main classes—B cells and T cells—which mediate humoral and cell-mediated immunity, respectively8
Mucosal: pertaining to the mucous tissue lining various tubular structures, consisting of epithelium, lamina propria, and in the digestive tract, a layer of smooth muscle7
T cell: a subset of lymphocytes defined by their development in the thymus and by heterodimeric receptors associated with the proteins of the CD3 complex8
Macrophages: large, migratory, mononuclear phagocytic cells important in innate immunity and in early nonadaptive phases of host defense; act as antigen-presenting cells and as effector cells in humoral and cell-mediated immunity8
Cytokines: proteins made by cells that affect the behavior of other cells; act via specific cytokine receptors on the cells that they affect8
Chemokine: small chemoattractant protein that stimulates the migration and activation of cells, especially phagocytic cells and lymphocytes8
Adhesion molecule: mediates the binding of one cell to other cells or to extracellular matrix proteins8