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P141. Mucosal cytokine profiles in early, untreated Crohn's disease

C.S. Horjus1, E.G. van Lochem2, L. Roovers1, D. de Jong3, R.J. Robijn1, M.J. Groenen1, P.J. Wahab1

1Rijnstate Hospital, Department of Gastroenterology, Arnhem, Netherlands; 2Rijnstate Hospital, Department of Immunology, Arnhem, Netherlands; 3Universitair Medisch Centrum St Radboud, Afd Maag–Darm Leverziekten, Nijmegen, Netherlands

Background: Little is known about the mucosal inflammatory profile of Crohn's disease (CD) at presentation and its implication for future course of disease. We aim to identify cytokine profiles at diagnosis that may correlate with clinical outcome during follow-up.

In this study we present early mucosal cytokine profiles in relation with endoscopic features.

Methods: Mucosal biopsies from inflamed colon and ileum were taken during ileocolonoscopy from patients presenting with the first attack of CD. The endoscopic disease activity was assessed using the Simple Endoscopy Score for Crohn's disease (SES-CD). T‑cells were isolated from the endoscopic biopsies and fenotyped by flowcytometry. After overnight stimulation, excreted levels of IL‑2, IL‑4, IL‑6, IL‑10, TNF alfa, IFN-gamma en IL‑17 were measured by flowcytometry. Cytokine concentrations were corrected for the number of isolated T‑cells.

Results: We prospectively included 34 CD patients (pt.) and 5 healthy controls. According to SES-CD, 12 pt. showed mild activity, 10 pt. moderate activity and 12 pt. severe activity at endoscopy. We identified three different cytokine profiles: a “low profile” (12 pt.) with TNF-alfa <1000 pg/ml, an “intermediate profile” (13 pt.) with TNF-alfa 1000–10000 pg/ml and a “high profile” (9 pt.) with TNF-alfa >10000 pg/ml. The median values of the cytokines in each group are shown in the table. As may be expected, controls express low to intermediate levels of cytokines. In the “low profile” CD group, TNF-alfa, IL‑2, IL‑4 and IL‑6 but not the IL‑17 and IFN-gamma levels are lower than in controls. There was no significant correlation between the cytokine profiles and the endoscopic disease activity.

Cytokine profileTNF-alfaIFN-gammaIL‑17IL‑2IL‑4IL‑6IL‑10

Conclusions: CD patients express different cytokine profiles at diagnosis, independent of the severity of the endoscopic disease activity. These profiles show relative high levels of TNF-alfa and IFN-gamma and moderately elevated levels of IL‑17 suggesting a strong Th1 and a moderate Th17 response. Interestingly, we see a patient group with a lower than normal cytokine expression. Maybe these patients will prove to be less sensitive for immunosuppressive therapy.