Elevated interleukin-8 in bile of patients with primary sclerosing cholangitis

S. J. Zweers, A. Shiryaev, M. Komuta, M. Vesterhus, J.R. Hov, M.J. Perugorria, D.R. de Waart, J.C. Chang, S. Tol, A.A. Te Velde, W.J. de Jonge, J.M. Banales, T. Roskams, U. Beuers, T.H. Karlsen, Peter L.M. Jansen, Frank G. Schaap*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: To better understand the pathogenesis of primary sclerosing cholangitis, anti- and pro-inflammatory factors were studied in bile. METHODS: Ductal bile of PSC patients (n=36) and controls (n=20) was collected by endoscopic retrograde cholangiography. Gallbladder bile was collected at liver transplantation. Bile samples were analyzed for cytokines, FGF19 and biliary lipids. Hepatobiliary tissues of PSC and non-PSC patients (n=8-11 per patient group) were collected at transplantation and were analyzed for IL8 and FGF19 mRNA expression and IL8 localization. The effect of IL8 on proliferation of primary human cholangiocytes and expression of pro-fibrotic genes was studied. RESULTS: In PSC patients, median IL8 in ductal bile was 6.6 ng/mL vs. 0.24 ng/mL in controls. Median IL8 in gallbladder bile was 7.6 ng/mL in PSC vs. 2.2 and 0.3 ng/mL in two control groups. IL8 mRNA in PSC gallbladder was increased and bile ducts stained positive for IL8. In vitro, IL8 induced proliferation of primary human cholangiocytes and increased the expression of pro-fibrotic genes. CONCLUSION: Elevation of IL8 in bile of PSC patients, collected at different stages of disease, indicates an on-going inflammatory stimulus that drives IL8 production. This challenges the idea that advanced PSC is a burned-out disease, and calls for reconsideration of anti-inflammatory therapy in PSC. This article is protected by copyright. All rights reserved.
Original languageEnglish
Pages (from-to)1370-1377
Number of pages8
JournalLiver International
Volume36
Issue number9
DOIs
Publication statusPublished - Sep 2016

Keywords

  • bile
  • gallbladder
  • interleukin 8
  • primary sclerosing cholangitis
  • BILIARY EPITHELIAL-CELLS
  • HEPATITIS-C
  • T-CELLS
  • EXPRESSION
  • IL-8
  • LIVER
  • ACTIVATION
  • IMMUNITY

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