The pathophysiologic rationale for biological therapies in inflammatory bowel disease

John N. Gordon, Antonio Di Sabatino, Thomas T. MacDonald

Research output: Contribution to journalArticle

Abstract

Purpose of review: Inflammatory bowel disease is driven by an excessive immune response in the gut wall. This review summarises important new developments in understanding this immune response and the downstream mechanisms of intestinal injury, alongside their potential role in opening up new avenues of treatment. Recent findings: The evidence continues to accumulate that Crohn's disease is primarily due to a T helper cell-type 1 immune response in the gut wall. IL-12 and IL-18 appear to be the cytokines primarily responsible for Th1 polarisation, but IL-21 may also be important. The p40 chain of IL-12 also associates with a novel p19 chain to form IL-23 which is also a potent Th1-inducing cytokine but the expression of IL-23 in Crohn's disease has not been reported. Progress in understanding the immunology of ulcerative colitis remains slow, but IL-13 produced by natural killer T cells may be involved. T-cell resistance to apoptosis occurs in Crohn's disease, and human and mouse studies indicate that the signalling molecule STAT3, which transduces signals from IL-6 and IL-10, is involved in mucosal T cell homeostasis. Fibroblasts and metalloproteinases continue be implicated in ulceration, fibrosis, and fistula formation. Summary: Understanding the immunology of inflammatory bowel disease continues to underpin the vast majority of new therapies and identifies new targets. Novel approaches, such as exploiting the antiinflammatory role of cannabinoid receptors, may also prove productive in the future.

Original languageEnglish
Pages (from-to)431-437
Number of pages7
JournalCurrent Opinion in Gastroenterology
Volume21
Issue number4
Publication statusPublished - Jul 2005

Keywords

  • Apoptosis
  • Crohn's disease
  • Interleukin-12
  • Interleukin-13
  • Metalloproteinase
  • Proteinase activated receptor
  • STAT3
  • T cells
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology

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