In inflammatory bowel disease, the uncontrolled inflammatory response to antigens in the gut is partly the result of an immune system dysfunction. This dysregulation may at least in part depend in an imbalance of mucosal inflammatory (TH1, TH2) cells and counter regulatory cells (IL-10, TGF–ß1, PGE2) (1).
In animal models, T Helper cells, as mediators of inflammation, produce different patterns of cytokines that cause mucosal tissue damage (1). In IBD, an excessive T-Helper 2 (TH2) response results in strong antibody responses and plays an important role in reactivity against allergens and helminthic infections (1). A marked increase in IgG1 antibodies, which are capable of activating the complement cascade, has been observed in the mucosa of ulcerative colitis patients (1). The majority of patients with ulcerative colitis (60%-80%) have serum and mucosal IgG antibodies against p-ANCA and colonic epithelial antigens (i.e., the cytoskeletal proteins tropomyosins) (1).
An excess production of IL-1ß, IL-6, IL-8, IL-16, and TNF-α is noted in the ulcerative colitis mucosa (1). The biological activities of TNF-α, in particular, are broad and contribute directly and indirectly to intestinal inflammation and damage (1). TNF-α has been shown to activate macrophages, promote the release of other pro-inflammatory cytokines and mediators (nitric oxide, prostacyclin, platelet-activating factor), promote the recruitment of new inflammatory cells into the mucosa by inducing the expression of adhesion molecules on vascular endothelium (1, 2). TNF-α can also induce morphologic changes in the epithelial membranes by stimulating gut fibroblasts to synthesize matrix metalloproteinases (MMPs) (1).
Glossary
Cytokines
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner (3).
IL
Interleukin are of the larger class of T-cell products, now frequently considered as cytokines. Interleukins, of which there are twelve identified to date, modulate inflammation and immunity by regulating growth, mobility, and differentiation of lymphoid and other cells. Included among the cytokines are cachectin and lymphotoxin, which are now known as tumor necrosis factor-alpha and tumor necrosis factor-beta, respectively (4).
INF-γ
is a dimerized soluble cytokine which is a Type II Interferon. In contrast to interferon-alpha and interferon-beta which can be expressed by all cells, INF- γ is secreted by T lymphocytes and NK cells only.
p-ANCA
Perinuclear antineutrophil cytoplasmic antibodies.
TNF-α
Tumor necrosis factor-alpha; an important cytokine produced by activated macrophages and T cells involved in systemic inflammation and the acute phase response.
- Pallone F, Monteleone G, Monteleone I, Biancone L. The immune system in inflammatory bowel disease. In Satsangi J, Sutherland LR, eds. Inflammatory Bowel Diseases. London: Churchill Livingstone. Elsevier Limited, 2003: 85-93.
- Hanauer, SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflammatory Bowel Disease:2006;12(suppl 1):S3-S12.
- On-line Medical Dictionary. Available at: http://cancerweb.ncl.ac.uk/cgi-bin/omd?query=cytokines. Accessed August 25, 2006.
- On-line Medical Dictionary. Available at: http://cancerweb.ncl.ac.uk/cgi-bin/omd?query=interleukin. Accessed August 25, 2006.