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Gastroenterology. 2011 May;140(6):1756-67. doi: 10.1053/j.gastro.2011.02.016.

Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases.

Author information

  • 1Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. wstrober@niaid.nih.gov

Abstract

The cytokine responses characterizing the inflammatory bowel diseases are the key pathophysiologic elements that govern the initiation, evolution, and, ultimately, the resolution of these forms of inflammation. Studies during the last 2 decades now provide a detailed (but not yet complete) picture of the nature of these responses. The first tier of cytokine responses are governed by the T-cell differentiation patterns dominating the disease. In Crohn's disease, the major cytokines arise from T-helper cell (Th) 1 and Th17 CD4(+) T-cell differentiation and consist of interferon-γ and interleukin (IL)-17/IL-22 generated by these types of differentiation. The relative importance of these cytokines to Crohn's inflammation is still unclear, although evidence is mounting that interferon-γ is primus inter pare (first among equals). In contrast, in ulcerative colitis, a Th2-like differentiation process is paramount, which results in expansion of natural killer T cells producing IL-13 (and perhaps IL-5). These disease-specific cytokine patterns give rise to a second tier of cytokines that span the Th1/Th17-Th2 divide and act as upstream facilitators and downstream mediators of inflammation. These cytokines include the well-known tumor necrosis factor-α, IL-1β, IL-6 triumphirate, as well as a more recently studied cytokine known as TL1A (tumor necrosis factor-like ligand). In this review, we will explore this cytokine landscape with the view of providing an understanding of how recent and future anticytokine therapies actually function.

Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID:
21530742
[PubMed - indexed for MEDLINE]
PMCID:
PMC3773507
Free PMC Article

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