Inflammatory Properties of Ileal Fluid from Patients with IBD
Florian Kuehn, Yang Liu, Enyu Liu, Robin Vasan, Fatemeh Adiliaghdam, Juan M. Ramirez, Matthew Farber, Alexander R. Munoz, Sulaiman R. Hamarneh, Richard A. Hodin
Department of Surgery, Massachusetts General Hospital, Boston, USA
Background: Patients with Crohn´s disease benefit from intestinal diversion, with immediate recurrence of inflammation after stoma reversal. Furthermore, pouchitis in ulcerative colitis does not occur prior to restoration of continuity. These observations suggest that exposure to factors within the fecal stream is a critical component in inciting phenotypic expression of IBD. Recently, the anti-inflammatory mucosal defense factor intestinal alkaline phosphatase (IAP) was linked to IBD.
Methods: Ileostomy effluent was assayed by ELISA for key pro-inflammatory cytokines. Human THP1 macrophages were exposed to the fluid and assayed for cytokine expression. IAP-activity was measured using the para-Nitrophenylphosphate (pNPP) assay. Patient characteristics were correlated with inflammatory properties.
Results: Ileal fluid from 23 patients with a median age of 56 years (range; 29-94) was collected and assayed. TNF-alpha levels were significantly higher in ileal fluid of IBD patients than in controls (92.1 ± 29.9pg/ml vs. 33.6 ± 9.4pg/ml; p = 0.03) whereas IL-8 levels were similar (50.1 ± 11.9 vs. 35.3 ± 7.4; p > 0.05). IAP-activity was significantly lower in patients with IBD than in patients without underlying inflammatory disease (14.6 ± 1.4 U/mg protein vs. 23.3 ± 2.2 U/mg protein; p=0.002). THP1 cell response exposed to ileal fluid showed an individual cytokine profile for each patient and did not correlate with the cytokine levels in the original sample.
Conclusion: Ileal fluid of IBD patients contained significantly higher TNF-alpha levels and lower IAP-activity. The individual inflammatory response profile could serve as a basis for determining the risk for recurring disease or pouchitis in stoma patients with IBD.
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