P0122 The Potential Role of Circulating Cytokines and Chemokines To Predict Intestinal Failure in Patients Affected by Short Bowel Syndrome
Authors: Di Mattia M , Pane C , Petito V , Profeta F , Foscarini E , Lamolinara A , Iezzi M , Troisi S , Masi L , Emoli V , Becherucci G , Turchini L , Gasbarrini A , Papa A , Scaldaferri F , Lopetuso L R 
Published: January 2025

Background

Short bowel syndrome (SBS) is a life-altering and life-threatening disease resulting from massive small bowel resections, often occurring in patients with Crohn's disease (CD), a severe chronic gastrointestinal disorder characterized by the infiltration of inflammatory cells into the intestinal mucosa and submucosa. Several cytokines and chemokines play a crucial role in the development and progression of inflammatory bowel disease by recruiting inflammatory cells1,2. Currently, no biomarkers indicate a higher risk of developing SBS or intestinal failure (IF); thus, the present study aims to evaluate the circulating cytokine/chemokine profile in patients affected by IF/SBS and CD patients at high risk of developing IF, to identify disease severity-related biomarkers.

Methods

A total of 150 CD patients were enrolled in this study, and they were stratified into four subgroups based on the disease severity: SBS patients with IF and parenteral nutrition (A1 group) or without IF and inactive disease (A3 group); CD patients with high (B group) or low risk of IF (C2 group). Circulating cytokines and chemokines levels were determined using the human 27-PLEX assay on sera collected from patients at the moment of the enrollment (T0, n=70) and after 6 months (T6M, n=10).

Results

Among inflammatory cytokines, high levels of RANTES, PDGF-BB, IP-10, MIP-1β, IL-9, and EOTAXIN were detected in all groups, while the levels of anti-inflammatory interleukins such as IL-4 and IL-13 resulted low in all patients at T0 (fig.1). At T6M, a general reduction of all the enhanced inflammatory markers was detected in all the groups except for RANTES, whose levels were almost unchanged and even increased in the A3 group. On the contrary, IP-10, which appears explicitly increased in the A1 group, is the most significantly reduced in all groups at T6M (fig.2).

Conclusion

Our results show a difference in the levels of circulating cytokines/chemokines profiles among the different groups of patients. In particular, IP-10, EOTAXIN, and PDGF-BB are significantly higher in the A1, A3, and C2 groups, respectively, while IL-9, RANTES, and MIP-1β levels present a similar profile at T0. After 6 months, a general reduction of all the analyzed inflammatory markers was recorded in all the groups. In particular, IP-10 shows the most relevant reduction, while RANTES levels remain almost unaltered at T6M. Literature data confirmed a role for these cytokines/chemokines in CD severity and progression3,4. However, to validate these preliminary data and potentially find a biomarker for IF prediction, more samples will be collected and analyzed.

References

1.Friedrich M, Pohin M, Powrie F. Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. Immunity. 2019;50(4):992-1006. doi:10.1016/j.immuni.2019.03.017

2.Singh UP, Singh NP, Murphy EA, et al. Chemokine and cytokine levels in inflammatory bowel disease patients. Cytokine. 2016;77:44-49. doi:10.1016/j.cyto.2015.10.008

3.Mello JDC, Gomes LEM, Silva JF, et al. The role of chemokines and adipokines as biomarkers of Crohn’s disease activity: a systematic review of the literature. Am J Transl Res. 2021;13(8):8561-8574.

4.Ansari N, Abdulla J, Zayyani N, Brahmi U, Taha S, Satir AA. Comparison of RANTES expression in Crohn’s disease and ulcerative colitis: an aid in the differential diagnosis? J Clin Pathol. 2006;59(10):1066-1072. doi:10.1136/jcp.2005.034983