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The last decade has seen rapid developments in the field of biological therapy for inflammatory bowel disease (IBD). Understanding the immunopathogenesis of IBD has led to identification of distinct immunological targets. Such targeted therapy with antitumour necrosis factor (TNF) monoclonal antibodies is now in widespread use for both Crohn’s disease (CD) and ulcerative colitis (UC). Beyond this, therapies with other anticytokines are in various stages of development, including antibodies against interleukin 6 (IL6), IL12/23 and interferon γ (IFNγ).
The rationale for targeting these cytokines is largely derived from observations regarding the cytokine profile in intestinal tissues from patients with generally long-standing IBD, and from experiments utilising animal models of the disease. Analysis of the mucosal T cell phenotype had until recently largely supported the concept of CD as a Th1 disease, driven by IL12 and characterised by the production of the signature cytokine, IFNγ, and UC as an atypical Th2 disease characterised by production of cytokines such as IL13. More recently, the discovery of the Th17 lineage, driven by IL23 (as well as IL6 and transforming growth factor β) and characterised by IL17 production has led to a re-evaluation, and the realisation that a number of inflammatory conditions in which Th1 was previously considered central, may actually be Th17 dependent. Amongst these are several experimental models of colitis, and there is emerging evidence of CD as a Th17 disease. To add to the complexity, in contrast to mice, in humans a significant proportion of Th17 cells also secrete IFNγ, thus displaying a mixed Th17/Th1 cytokine phenotype, particularly in the gut.1 Furthermore, a number of observations regarding Th17 cells challenge our concepts of terminal T cell lineage commitment, with the demonstration that regulatory T cells can differentiate into inflammatory Th17 cells.2 A number of …
Funding: SG’s department has received funding for research from the National Association of Colitis and Crohn’s disease (NACC) and Broad Medical Research Foundation.
Competing interests: None.
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