title: Interleukin-6 is associated with steroid resistance and reflects disease activity in severe pediatric ulcerative colitis.
abstract: OBJECTIVE
  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.
authors: Department of Pediatrics, University of Alberta, Edmonton, AB, Canada. Electronic address: wine@ualberta.ca.
authors: Eytan
authors: E
authors: Wine
authors: David R
authors: DR
authors: Mack
authors: Jeffrey
authors: J
authors: Hyams
authors: Anthony R
authors: AR
authors: Otley
authors: James
authors: J
authors: Markowitz
authors: Wallace V
authors: WV
authors: Crandall
authors: Neal
authors: N
authors: Leleiko
authors: Aleixo M
authors: AM
authors: Muise
authors: Anne M
authors: AM
authors: Griffiths
authors: Dan
authors: D
authors: Turner
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D004351:Drug Resistance; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D015999:Multivariate Analysis; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6
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