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P030. Mucosal cytokine profiles in inflammatory bowel disease patients

G. Roda, A. Sartini, M. Marocchi, A. Belluzzi, A. Caponi, G. Rosati, G. Ugolini, A. Roda, E. Roda, G. Mazzella

University of Bologna, Bologna, Italy

Aim: The intestinal immune system generates specific inflammatory and non-inflammatory states in response to such various luminal antigens by producing thousands of different cytokines.

The knowledge of how locally-produced cytokines may contribute to the development and maintenance of Inflammatory Bowel Disease (IBD) is crucial for new drug targets discovery. This study wants to define specific cytokines profiles in IBD patients, to determine if it is possible to modify this fingerprint in presence of specific drugs with the aim to sewing personal therapy based on the citokine profile of each patient at a given time.

Materials and Methods: 45 patients (15 controls undergoing non-IBD surgical procedures, 15 Crohn's Disease – CD – and 15 Ulcerative Colitis – UC) were prospectively included in the study. Biopsy specimens were collected from surgical resection or from the endoscopy suite and used for experiments because representative of a conserved microenvironment. Tissues were incubated for 24 hours at 37°C in different conditions. Culture tissue supernatants were collected and cytokine concentrations were assessed with multiplex ELISA immunoassay for 10 cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12 (p70), IL-13, IL-17, IFN-γ and TNF-α).

Results: CD group showed significantly (p < 0.05) increased levels of Th1-type cytokines (IL-1β, IL-2, IL-6, IFN-γ and TNF-α); increased levels of IL-4, IL-10 and IL-13 were detected in UC supernatants (p < 0.05).

IL-1β, IL-6, TNF-α levels were significantly increased in histologically active specimen, in both controls (peritumoral areas) and IBD groups (p < 0.05).

IL-12 and IL-17 were increased in both CD and UC compared to controls (p < 0.05).

The incubation with an anti-TNF-α monoclonal antibody determined a reduction of all the Th1-cytokines downstream of TNF-α, while TNF-α levels do not appear to undergo changes.

Conclusion: In conclusion, our study represents the first simultaneous approach to the evaluation of the mucosal cytokines production. We demonstrated a consistent difference between disease and healthy microenvironment and between active and inactive disease. Our data confirm that CD has a typical Th1-type cytokine profile, and UC shows levels of IL-4, IL-10 and IL-13. At the same time, thanks to multiplex ELISA analysis we observed a group of IBD-specific cytokines, such as IL-12 and IL-17, which are probably the main responsible for tissue specific damage seen in IBD.

Thanks to the evaluation of single patient cytokine profiles, personalized therapies or new drugs direct towards specific pathways could be developed.

Moreover, understanding how anti-TNF-α agents modify the local citokines profile of each patient may explain the lack/loss of efficacy of biological drugs in some patients.