Correlation of ex vivo cytokine secretion profiles with scoring indices in ulcerative colitis

BACKGROUND In ulcerative colitis, the complexity of mucosal cytokine secretion profiles and how they correlate with endoscopic and clinical scores is still unclear. METHODS In this study, we collected fresh biopsies from UC patients to investigate which cytokines are produced in ex vivo culture conditions, a platform increasingly used for testing of novel drugs. Then, we correlated cytokine production with several scoring indices commonly used to assess the severity of the disease. RESULTS Increased levels of IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNFα and IFNɣ were produced by biopsies of UC patients compared to non-IBD controls. Our results show a better correlation of cytokine levels with Mayo Endoscopic Subscore (MES) and Mayo score, than the more complex Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Out of 10 measured cytokines, eight correlated with MES, six with Mayo score and only three with UCEIS, due to the partial increase in cytokine secretion observed in donors with UCEIS = 7-8. When we analysed individual subscores within the UCEIS, Vascular Network subscore showed a correlation similar to MES (7/10 cytokines), while Bleeding as well as Erosions and Ulcers subscores correlated with only 3/10 cytokines, similarly to the total UCEIS. CONCLUSIONS Our findings suggest that choosing biopsies from donors with MES = 2-3 and UCEIS = 2-6 from areas with no bleeding and no superficial and/or deep ulcers could enable a deeper insight into the cytokine profile of the inflamed tissue and represent a better tool for studying potential therapeutic targets and evaluation of novel therapies.

[1]  R. Corcoran,et al.  Association Between Ex Vivo Human Ulcerative Colitis Explant Protein Secretion Profiles and Disease Behaviour , 2022, Digestive Diseases and Sciences.

[2]  H. Nakase,et al.  The influence of cytokines on the complex pathology of ulcerative colitis. , 2021, Autoimmunity reviews.

[3]  A. Giuliani,et al.  IL-13 mRNA tissue content identifies two subsets of adult ulcerative colitis patients with different clinical and mucosa-associated microbiota profiles. , 2020, Journal of Crohn's & colitis.

[4]  M. Murad,et al.  First- and Second-line Pharmacotherapies for Patients with Moderate to Severely Active Ulcerative Colitis: An Updated Network Meta-Analysis. , 2020, Clinical Gastroenterology and Hepatology.

[5]  L. Öhman,et al.  Mucosal and systemic immune profiles differ during early and late phase of the disease in patients with active ulcerative colitis. , 2019, Journal of Crohn's & colitis.

[6]  Asher Mullard,et al.  Parsing clinical success rates , 2016, Nature Reviews Drug Discovery.

[7]  Markus F. Neurath,et al.  Cytokines in inflammatory bowel disease , 2014, Nature Reviews Immunology.

[8]  D. Altman,et al.  Reliability and initial validation of the ulcerative colitis endoscopic index of severity. , 2013, Gastroenterology.

[9]  M. Yamazaki,et al.  Interleukin-13 damages intestinal mucosa via TWEAK and Fn14 in mice-a pathway associated with ulcerative colitis. , 2011, Gastroenterology.

[10]  D. Altman,et al.  Translational Gastroenterology , 2011 .

[11]  G. Roda,et al.  Cytokine Networks in Ulcerative Colitis , 2011 .

[12]  Y. Sagiv,et al.  Interleukin 2 targeted therapy in inflammatory bowel disease , 2009, Gut.

[13]  D. Bernardo,et al.  High Levels of Proinflammatory Cytokines, but Not Markers of Tissue Injury, in Unaffected Intestinal Areas from Patients with IBD , 2009, Mediators of inflammation.

[14]  R. Marciniak,et al.  Proinflammatory cytokines and IL-10 in inflammatory bowel disease and colorectal cancer patients , 2009, Archivum Immunologiae et Therapiae Experimentalis.

[15]  S. Umemura,et al.  Quantitive Cytokine mRNA Expression Profiles in the Colonic Mucosa of Patients with Steroid Naïve Ulcerative Colitis During Active and Quiescent Disease , 2009, Inflammatory bowel diseases.

[16]  G. Ramadori,et al.  Quantitative measurement of cytokine mRNA in inflammatory bowel disease: relation to clinical and endoscopic activity and outcome , 2005, European journal of gastroenterology & hepatology.

[17]  T. Wynn IL-13 effector functions. , 2003, Annual review of immunology.

[18]  B. Vainer,et al.  Upregulation of Interleukin-12 and -17 in Active Inflammatory Bowel Disease , 2003, Scandinavian journal of gastroenterology.

[19]  W. Reinisch,et al.  Transfer of interleukin-4 and interleukin-10 in patients with severe inflammatory bowel disease of the rectum. , 2000, Human gene therapy.

[20]  S. Schreiber,et al.  Immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease. , 1995, Gastroenterology.

[21]  C. Hawkey,et al.  Plasma and tissue interleukin‐2 receptor levels in inflammatory bowel disease , 1990, Clinical and experimental immunology.

[22]  L. Sutherland,et al.  5-Aminosalicylic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis. , 1987, Gastroenterology.

[23]  T. Molnár,et al.  Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 2: Current Management. , 2017, Journal of Crohn's & colitis.