Interleukin‐8: A critical chemokine in biliary atresia

Dong, Rui; Zheng, Shan

doi:10.1111/jgh.12900

Cited by 52 publications

(42 citation statements)

References 73 publications

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“…The main function of IL‐8 is to act as a chemokine and promote neutrophil activation and migration to sites of inflammation (i.e., liver). Our finding of elevated IL‐8 as an immune marker for poor outcome is supported by studies showing that liver IL‐8 levels correlated with liver inflammation, fibrosis, and portal hypertension in BA . Activated neutrophils produce potent byproducts that can directly or indirectly damage cells and include elastase, MPO, and NETs .…”

Section: Discussionsupporting

confidence: 74%

“…Our finding of elevated IL-8 as an immune marker for poor outcome is supported by studies showing that liver IL-8 levels correlated with liver inflammation, fibrosis, and portal hypertension in BA. (38)(39)(40) Activated neutrophils produce potent byproducts that can directly or indirectly damage cells and include elastase, MPO, and NETs. (34)(35)(36)(37) IL-8-activated neutrophils have also been shown to promote fibrosis through activation of stellate cells.…”

Section: Discussionmentioning

confidence: 99%

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Correlation of Immune Markers With Outcomes in Biliary Atresia Following Intravenous Immunoglobulin Therapy

et al. 2019

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Biliary atresia is a progressive fibroinflammatory cholangiopathy of infancy that is associated with activation of innate and adaptive immune responses targeting bile ducts. A recently completed multicenter phase I/IIA trial of intravenous immunoglobulin in biliary atresia did not improve serum total bilirubin levels at 90 days after hepatoportoenterostomy or survival with the native liver at 1 year. A mechanistic aim of this trial was to determine if the peripheral blood immunophenotype was associated with clinical outcomes. Flow cytometry of peripheral blood cell markers (natural killer [NK], macrophage subsets, T‐ and B‐cell subsets, regulatory T cells), neutrophils, and activation markers (clusters of differentiation [CD]38, CD69, CD86, human leukocyte antigen‐DR isotype [HLA‐DR]) was performed on 29 patients with biliary atresia at baseline and at 60, 90, 180, and 360 days after hepatoportoenterostomy. Plasma cytokines and neutrophil products were also measured. Spearman correlations of change of an immune marker from baseline to day 90 with change in serum bilirubin revealed that an increase in total bilirubin correlated with 1) increased percentage of HLA‐DR + CD38 + NK cells and expression of NK cell activation markers CD69 and HLA‐DR, 2) decreased percentage of regulatory T cells, and 3) increased interleukin (IL)‐8 and associated neutrophil products (elastase and neutrophil extracellular traps). Cox modeling revealed that the change from baseline to day 60 of the percentage of HLA‐DR + CD38 + NK cells and plasma IL‐8 levels was associated with an increased risk of transplant or death by day 360. Conclusion: Poor outcomes in biliary atresia correlated with higher peripheral blood NK cells and IL‐8 and lower regulatory T cells. Future studies should include immunotherapies targeting these pathways in order to protect the biliary tree from ongoing damage.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Correlation of Immune Markers With Outcomes in Biliary Atresia Following Intravenous Immunoglobulin Therapy

et al. 2019

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“…IL8 is a multifunctional pro‐inflammatory cytokine that attracts neutrophils and regulates neutrophil activity . Upon prolonged presence IL8 may induce tissue damage . Our study shows that in PSC, IL8 levels in ductal and gallbladder bile are up to two orders of magnitude higher than in serum.…”

Section: Discussionmentioning

confidence: 73%

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

Zweers

Shiryaev

Komuta

et al. 2016

Liver International

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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.

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“…7 During this procedure, the bile flow is restored through the excision of extrahepatic biliary remnants, and a hepatic portoenterostomy reconstructs the bile duct to a jejunal loop. Several serum metabolites or proteins, like hyaluronic acid, 12 apolipoprotein C3, 13 interleukin 6, and interleukin 8, 14,15 have been reported to change in BA. [8][9][10][11] Recently, great efforts have been made to search for new biomarkers for BA.…”

Section: Introductionmentioning

confidence: 99%

Gut microbial profile in biliary atresia: a case‐control study

Wang

Tian

Jiang

et al. 2019

J of Gastro and Hepatol

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Background and Aim Biliary atresia (BA) is a progressive fibro‐inflammatory cholangiopathy with an unclear etiology. Various liver disorders are associated with an altered microbiome. However, gut microbiome in BA remains unknown. Here, we performed a case‐control study to investigate the gut microbiota in BA. Methods A cross‐sectional analysis was first conducted for 34 BA patients and 34 healthy controls. Then we investigated the shift in gut microbiota 2 weeks after the Kasai procedure in 16 BA patients. Gut microbiome was initially analyzed using 16S ribosome RNA gene sequencing and further validated by metagenomic sequencing. Fecal bile acids were determined using ultra‐high performance liquid chromatography. Results Compared with healthy controls, BA showed lower diversity and significant structural segregation in the microbiome. At phylum level, Proteobacteria numbers increased, whereas those of Bacteroidetes decreased in BA. At genus level, several potential pathogens such as Streptococcus and Klebsiella thrived in BA, while numbers for Bifidobacterium and several butyrate‐producing bacteria declined. The microbiome was also disturbed after the Kasai procedure. Operational taxonomic units responding to BA showed significant correlation with liver function. Furthermore, the abundance ratio of Streptococcus/Bacteroides showed great promise in distinguishing BA from healthy controls. Intestinal bile acids were dramatically decreased in BA, and Clostridium XIVa positively correlated with the ratio of primary/secondary bile acids. Conclusions Gut microbial dysbiosis, may be caused by decreased bile acids, was associated with liver function and had a good diagnostic potential for BA. Therefore, further exploration of gut microbiota may provide important insights into their potential diagnostic and therapeutic benefits.

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Interleukin‐8: A critical chemokine in biliary atresia

Cited by 52 publications

References 73 publications

Correlation of Immune Markers With Outcomes in Biliary Atresia Following Intravenous Immunoglobulin Therapy

Correlation of Immune Markers With Outcomes in Biliary Atresia Following Intravenous Immunoglobulin Therapy

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

Gut microbial profile in biliary atresia: a case‐control study

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