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What Causes Crohn's?

Helper T cells are further categorized as TH1 and TH2. An imbalance in these two types appear to occur in IBD, although each disorder has a different balance:

• Ulcerative colitis patients favor a TH2 response, which activates the interleukins IL-5, IL-6, and IL-10. These mostly affect mucosal areas in the intestine.
• Research indicates that patients with Crohn's disease have increased activity in TH1 helper cells, activating interleukin-2 (IL-2) and interferon-gamma, which affect intestinal cells. Tumor necrosis factor (TNF) may be a particularly potent immune factor in Crohn's disease. It is important in properties that regulate inflammation and cell proliferation. If genetic or other factors increase production of this immune compound, it can lead to great harm.

Interleukin 6 appears to play a part in both IBDs, by inhibiting a natural mechanism called apoptosis, a process whereby cells self-destruct. In such cases, cells proliferate faster than they die, causing an excessively strong immune response.

Adhesion Molecules. Increased levels of certain molecules called E-selectin and intercellular adhesion molecule-1 (ICAM-1) also appear to play a major role in the inflammatory process by causing damaging immune factors to accumulate on intestinal cells. E-selectin may be involved in the early stages of the disease (especially ulcerative colitis) and ICAM-1 in the persistence of either inflammatory bowel disease.

Matrix Metalloproteinase. Greater activity of enzymes called matrix metalloproteinase has been detected in the colons of patients with IBD. Such increased levels tend to break down the extracellular matrix, a barrier composed of structural proteins and elastic fibers that surrounds and supports cells, in this case in the colon. Researchers suggest that this activity may cause persistent damage once the inflammatory process has triggered IBD.

Genetic Factors

Although the causes of inflammatory bowel disease are not yet known, genetic factors certainly play some role. Between 10 - 20% of people with ulcerative colitis have family members with the disease. Several candidate genes and chromosome locations have been identified that might prove to play a role in the development of ulcerative colitis, Crohn's disease, or both. Genetic factors appear to be more important in Crohn's disease, although there is evidence that they may have genetic defects in common. In either case, multiple genetic factors are likely to be responsible for susceptibility to these disorders.

Specific Genes Involved. One of the most important genetic discoveries to date was the identification of a genetic variant called NOD2, which appears to alter the immune system so that it launches an over-reaction in response to bacteria, causing inflammation. This genetic factor might be involved in 15% of Crohn's disease cases. Those with one copy of the mutated gene have twice the average risk of developing Crohn's, and those with two defective genes face 20 - 40 times the risk.