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P081 Resolvin D2 attenuates colonic inflammation of Crohn’s disease patients

Pascoal, L.B.(1);Palma, B.B.(1);Chaim, F.H.(1);Nogueira, G.(2);Rodrigues, B.L.(1);Ayrizono, M.L.S.(1);Velloso, L.A.(2);Leal, R.F.(1);

(1)University of Campinas UNICAMP, Inflammatory Bowel Disease Research Laboratory- Gastrocenter- Colorectal Surgery Unit- School of Medical Sciences, Campinas, Brazil;(2)University of Campinas UNICAMP, Laboratory of Cell Signaling- School of Medical Sciences, Campinas, Brazil

Background

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. Usually, the clinical management are based on sulphasalazine, corticosteroid, immunomodulators, biologics therapy and bioactive small molecules. However, new therapeutic strategies involving the inflammatory process are being proposed as the use of pro-resolution lipid mediators. This study aimed to investigate the potential therapeutical role of Resolvin D2 (RvD2) in the intestinal mucosa of CD patients and its therapeutic potential.

Methods

The study included 16 CD patients, 8 patients in remission (CDR) and 8 with active disease (CDA) and 6 healthy subjects in the control group (CTR); all were followed up in tertiary referral hospital. Blood sample and colonic biopsies were collected during colonoscopy. Disease activity was determined by the Crohn's Disease Endoscopic Index of Severity (CDEIS).  The serum blood level of RvD2 was determined by enzymatic immunosorption assay (ELISA). Intestinal biopsies were submitted to cell culture and treated with Infliximab (IFX) or RvD2. The expression of inflammatory cytokines was evaluated by real-time PCR and RvD2 levels through the ELISA. A nonparametric test was used for statistical analysis, with adopted p<0.05. The study was approved by the University of Campinas research ethics committee.

Results

The intestinal mucosa of the CDA group showed higher levels of pro-inflammatory markers, such as, IL1β (p=0.008 and p=0.01), IL6 (p=0.002), IL23 (p=0.03) and S100A8 (p=0.004 and p=0.01), compared to CTR and CDR groups, respectively. Although serum RvD2 levels of CDA (p=0.002) and CDR (p=0.004) groups were increased when compared to the CTR group, there is no differences between CDA and CDR groups (p>0.05). However, intestinal explants of the CDA group treated with RvD2 showed a significantly decrease of IL1β expression (p<0.05) when compared to the non-treated biopsies in the ex vivo culture experiments, similar to what was as verified by IFX treatment (p<0.05). 

Conclusion

The results suggest the participation of RvD2 in the modulation of colonic inflammation associated with CD. RvD2 showed to be as effective as IFX in attenuating the pro-inflammatory response present in the intestinal mucosa of patients with CD and provide insights into pro-resolution lipid mediators approaches to modulate chronic inflammation.

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