Interleukin-6 is associated with steroid resistance and reflects disease activity in severe pediatric ulcerative colitis |
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| Affiliation: | 1. Department of Pediatrics, University of Alberta, Edmonton, AB, Canada;2. Children''s Hospital of Eastern Ontario, Ottawa, ON, Canada;3. Connecticut Children''s Medical Center, Hartford, CT, USA;4. Department of Pediatrics, Dalhousie University, Halifax, NS, Canada;5. Division of Pediatric Gastroenterology, Schneider Children''s Hospital, New Hyde Park, NY, USA;6. Division of Pediatric Gastroenterology, Hepatology and Nutrition, Nationwide Children''s Hospital, Columbus, OH, USA;7. Hasbro Children''s Hospital, Providence, RI, USA;8. Hospital for Sick Children, Toronto, ON, Canada;9. Pediatric Gastroenterology Unit, Shaare Zedek Medical Center, The Hebrew University, Jerusalem, Israel;1. IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel;2. Faculty of Natural Sciences, Lausitz University of Applied Sciences, Senftenberg, Germany;1. Colorectal Surgery Unit, Cajuru University Hospital, Catholic University of Parana, Curitiba, Brazil;2. Gastroenterology Unit, Cajuru University Hospital, Catholic University of Parana, Curitiba, Brazil;2. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana;3. Department of Neurology, Tongliao Municipal Hospital, Inner Mongolia, China;4. Department of Neurology, Kerqin District First People''s Hospital of Tongliao City, Inner Mongolia, China;5. Department of Neurology, the 88th Hospital of PLA, Shandong, China |
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| Abstract: | Background and aimApproximately one third of patients with acute severe ulcerative colitis (ASC) will fail intravenous corticosteroids (IVCS). Predicting response to IVCS to initiate early salvage therapy remains challenging. The aim of this study was to evaluate the role of serum inflammatory cytokines in ASC and determine their predictive utility with IVCS treatment failure.MethodsThis preplanned ancillary study, part of the prospective multicenter OSCI study, evaluated pediatric ASC in North America. Serum samples were obtained from 79 children admitted for ASC on the third day of IVCS treatment. Twenty-three (29%) patients required second-line therapy. ELISA-based cytokine arrays were used [TNF-α, IFN-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, and IL-17], selected based on a systematic literature search.ResultsIn univariate analysis, only IL-6 was significantly different between responders and non-responders (P = 0.003). The risk for IVCS failure increased by 40% per each pg/mL increase in IL-6 level. Factor analysis found IL-6 to be associated with IL-17, suggesting involvement of the T-helper (TH)17 pathway. In a multivariate analysis, disease activity [judged by the Pediatric UC Activity Index (PUCAI)] assumed all the association with the treatment outcome while IL-6 was no longer significant (P = 0.32; PUCAI score P < 0.001).ConclusionsWhile IL-6 strongly predicted IVCS failure, it likely reflects disease activity and not direct interference with corticosteroid pathway. Nonetheless, IL-6 levels may have a role in predicting IVCS response in severe pediatric UC for treatment decision-making or potentially in medical intervention by virtue of anti-IL-6 antibodies in severe UC. |
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