Interleukin-6 is associated with steroid resistance and reflects disease activity in severe pediatric ulcerative colitis

Abstract

Background and aim: Approximately 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.

Methods: This 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.

Results: In 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).

Conclusions: While 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.

Keywords: ASC; C-reactive protein; CRP; Disease marker; ESR; GR; IBD; IFN; IL; IQR; IVCS; Inflammatory bowel diseases; Methylprednisolone; OR; PGA; PUCAI; Pediatric UC Activity Index; Response to treatment; T(H); T-helper; TNF; UC; acute severe ulcerative colitis; erythrocyte sedimentation rate; glucocortocoid receptor; inflammatory bowel diseases; interferon; interleukin; interquartile range; intravenous corticosteroids; odds ratio; physician global assessment; tumor necrosis factor; ulcerative colitis.