Global mucosal and serum cytokine profile in patients with ulcerative colitis undergoing anti-TNF therapy

• Background and objective. The knowledge of the effects of anti-tumour necrosis factor (TNF) treatment on the global cytokine profile in patients with ulcerative colitis (UC) is limited. A better understanding of these mechanisms could improve the ability to select patients that should undergo the therapy. Therefore, the aim was to determine the global mucosal and serum cytokine profile before and during induction therapy with anti-TNF in UC patients. Materials and methods. In total, mucosal biopsies (n = 28) and serum samples (n = 42) were collected from UC patients (total n = 48) before anti-TNF therapy. At week 14 response to the therapy was evaluated and again mucosal biopsies (n = 14) and serum samples (n = 42) were collected. Quantitative real-time PCR was used to determine mucosal cytokine mRNA expression and the MSD MULTI-ARRAY assay system platform was used for analysis of cytokines in serum. The global cytokine profile was evaluated by multivariate factor analysis. Results. At baseline, the global profile of mucosal cytokine mRNA expression and serum cytokines discriminated therapy responders from non-responders. Responders had lower mucosal mRNA expression of interleukin 1 beta (IL-1 beta), IL-17A, IL-6 and interferon gamma (IFN-gamma) than non-responders. Fourteen weeks after therapy start mucosal IL-1 beta and IL-6 were down-regulated in therapy responders but not in non-responders. At week 14, serum levels of IL-6 were decreased in therapy responders whereas IFN-gamma and IL-12p70 were increased in non-responders. Conclusions. Our data suggest that patients with a therapy failure have a more severe pro-inflammatory cytokine profile before start of anti-TNF treatment, which is less well suppressed by the treatment as compared to therapy responders.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

adalimumab

biomarker

cytokine

IBD

infliximab

prediction

therapy response

ulcerative colitis

crohns-disease

infliximab therapy

gene-expression

maintenance

therapy

down-regulation

colonic-mucosa

in-vitro

t-cells

alpha

blood

Gastroenterology & Hepatology

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