title: Low expression of CXCR1/2 on neutrophils predicts poor survival in patients with hepatitis B virus-related acute-on-chronic liver failure.
abstract: Polymorphonuclear neutrophils (PMNs) and proinflammatory cytokines have been implicated in the pathogenesis of acute-on-chronic liver failure (ACLF). But the utility of CXC chemokine receptor expression on PMNs as a biomarker for prediction of disease severity is still uncertain. In this study, we investigated the dynamic expression of CXCR1 and CXCR2 on neutrophils, and found that patients with hepatitis B virus-related ACLF displayed low expression of CXCR1 and CXCR2 on peripheral neutrophils compared with healthy subjects and patients with chronic hepatitis B. This expression pattern was correlated with disease severity. Additionally, increased production of IL-8 in peripheral blood was significantly associated with reduced CXCR1 and CXCR2 expression, as shown by the decreased CXCR1 and CXCR2 expression on neutrophils after treating neutrophils with plasma from ACLF patients. This effect could be overcomed through IL-8 blockage with an anti-IL-8 antibody. We also found that IL-8 production and neutrophil infiltration were coordinately increased in the liver tissue of HBV-ACLF patients, and this increase was associated with liver inflammation. Overall, increased production of IL-8 associated with neutrophils infiltration into the liver and decreased CXCR1/2 expression on peripheral neutrophils. CXCR1 and CXCR2 expression levels could be served as early markers to predict the severity of ACLF.
authors.affiliation: Treatment and Research Centre for Infection Disease, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Ruonan
authors.initials: R
authors.lastname: Xu
authors.affiliation: The Institute of Clinical Examination Centre, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Bao
authors.affiliation: Treatment and Research Centre for Infection Disease, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Huihuang
authors.initials: H
authors.lastname: Huang
authors.affiliation: The Institute of Intensive Care Unit, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
authors.affiliation: Treatment and Research Centre for Infection Disease, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Treatment and Research Centre for Infection Disease, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Siyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Treatment and Research Centre for Infection Disease, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.affiliation: Treatment and Research Centre for Infection Disease, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Treatment and Research Centre for Infection Disease, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.affiliation: Treatment and Research Centre for Infection Disease, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Treatment and Research Centre for Infection Disease, Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000097:blood / Q000401:mortality; D000328:Adult; D015415:Biomarkers / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D005786:Gene Expression Regulation; D006509:Hepatitis B / Q000097:blood / Q000401:mortality; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D023062:Receptors, Interleukin-8A / Q000097:blood*; D023063:Receptors, Interleukin-8B / Q000097:blood*; D015996:Survival Rate
chemical_list: D015415:Biomarkers; C508606:CXCL8 protein, human; D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B