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 1β (IL-1β), IL-17A, IL-6 and interferon γ (IFN-γ) than non-responders. Fourteen weeks after therapy start mucosal IL-1β 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-γ 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.
['Dahlén|Rahil|R|', 'Magnusson|Maria K|MK|', 'Bajor|Antal|A|', 'Lasson|Anders|A|', 'Ung|Kjell-Arne|KA|', 'Strid|Hans|H|', 'Öhman|Lena|L|']
D000293:Adolescent D000328:Adult D000368:Aged D003093:Colitis, Ulcerative D016207:Cytokines D015536:Down-Regulation D005260:Female D006801:Humans D007413:Intestinal Mucosa D008297:Male D008875:Middle Aged D015999:Multivariate Analysis D012333:RNA, Messenger D060888:Real-Time Polymerase Chain Reaction D055815:Young Adult
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