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Liver Int. 2016 Sep;36(9):1370-7. doi: 10.1111/liv.13092. Epub 2016 Mar 16.

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

Author information

1
Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
2
Division of Cancer Medicine, Surgery and Transplantation, Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.
3
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
4
Division of Cancer Medicine, Surgery and Transplantation, Research Institute of Internal Medicine, K.G. Jebsen Inflammation Research Center, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
5
Morphology and Molecular Pathology, University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium.
6
National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway.
7
Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.
8
Department of Liver and Department of Gastrointestinal Diseases, Biodonostia Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), CIBERehd, Ikerbasque, San Sebasti√°n, Spain.
9
Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands.
10
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
11
Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.

Abstract

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, FGF19 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 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 ongoing 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.

KEYWORDS:

bile; gallbladder; interleukin 8; primary sclerosing cholangitis

PMID:
26866350
DOI:
10.1111/liv.13092
[Indexed for MEDLINE]

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