Interleukin-1 and interleukin-1 receptor antagonist in inflammatory bowel disease.
Ulcerative colitis (UC) and Crohn's disease (CD) are immunologically mediated disorders characterized by a chronic, relapsing inflammatory response. Elevation of several cytokines, with important immunoregulatory and proinflammatory activities have been demonstrated during active inflammatory bowel disease (IBD). These cytokines, including interleukin-1 (IL-1), IL-6, IL-8 and GM-CSF, may play an important role in the initiation and amplification of the inflammatory response leading to intestinal injury. There is increasing evidence that IL-1 is activated early in the cascade of events leading to inflammation. Therefore, IL-1 has been implicated as a primary target for therapeutic intervention for the treatment of several inflammatory diseases, including IBD. In addition, a mucosal imbalance of intestinal IL-1 and IL-1ra is present in patients with IBD, suggesting that insufficient production of endogenous IL-1ra may contribute to the pathogenesis of chronic gut inflammation. Preliminary studies examining the association between newly described polymorphisms in the IL-1 gene cluster and IBD have provided new insight into the genetic predisposition to UC. This article will review current progress in understanding the role of Il-1 and Il-1ra in IBD, as well as discuss recently described polymorphisms in the Il-1 gene cluster and their association with UC and CD.
Division of Gastroenterology an Hepatology, University of Virginia, Charlottesville 22908, USA.
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Cominelli
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Pizarro
D000818:Animals; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins