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Elevated interleukin‐8 in bile of patients with primary sclerosing cholangitis
Author(s) -
Zweers Serge J.,
Shiryaev Alexey,
Komuta Mina,
Vesterhus Mette,
Hov Johannes R.,
Perugorria María J.,
Waart D. Rudi,
Chang JungChin,
Tol Shanna,
Velde Anje A.,
Jonge Wouter J.,
Banales Jesus M.,
Roskams Tania,
Beuers Ulrich,
Karlsen Tom H.,
Jansen Peter L.,
Schaap Frank G.
Publication year - 2016
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13092
Subject(s) - primary sclerosing cholangitis , medicine , gastroenterology , gallbladder , liver transplantation , gallbladder stone , transplantation , disease
Background & Aims 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 analysed for cytokines, FGF 19 and biliary lipids. Hepatobiliary tissues of PSC and non‐ PSC patients ( n = 8–11 per patient group) were collected at transplantation and were analysed for IL 8 and FGF 19 mRNA expression and IL 8 localization. The effect of IL 8 on proliferation of primary human cholangiocytes and expression of pro‐fibrotic genes was studied. Results In PSC patients, median IL 8 in ductal bile was 6.6 ng/ml vs. 0.24 ng/ml in controls. Median IL 8 in gallbladder bile was 7.6 ng/ml in PSC vs. 2.2 and 0.3 ng/ml in two control groups. IL 8 mRNA in PSC gallbladder was increased and bile ducts stained positive for IL 8. In vitro, IL 8 induced proliferation of primary human cholangiocytes and increased the expression of pro‐fibrotic genes. Conclusion Elevation of IL 8 in bile of PSC patients, collected at different stages of disease, indicates an ongoing inflammatory stimulus that drives IL 8 production. This challenges the idea that advanced PSC is a burned‐out disease, and calls for reconsideration of anti‐inflammatory therapy in PSC .