title: Interleukin-21 is upregulated in hepatitis B-related acute-on-chronic liver failure and associated with severity of liver disease.
abstract: The immune mechanism(s) that lead to hepatitis B-related acute-on-chronic liver failure (HB-ACLF) are poorly understood. Interleukin-21 is a newly discovered cytokine that is involved in autoimmune and inflammatory diseases. Its potential role in HB-ACLF remains unknown. The serum levels of 12 immune cytokines measured by cytometric bead arrays and the frequency of IL-21-secreting CD4+ T cells in peripheral blood mononuclear cells (PBMC) measured by intracellular cytokine staining were compared in moderate chronic hepatitis B (M-CHB, n = 20), severe chronic hepatitis B (S-CHB, n = 20), HB-ACLF (n = 39) and healthy controls (n = 10). PBMC from M-CHB patients or healthy subjects were stimulated with rhIL-21 in vitro, and cytokines in supernatants were measured by FlowCytomix. The frequencies of IL-21-secreting CD4+ T cells were higher in HB-ACLF (both P < 0.001) and S-CHB (P = 0.002 and 0.001) as compared to M-CHB patients and controls. Serum IL-21 levels were highest (P < 0.001) in HB-ACLF and positively associated with high MELD score (P = 0.001) and mortality (P = 0.038). Recovery from HB-ACLF was associated with reduced serum IL-21 levels (P = 0.003) and lower CD4+ IL-21(+) T-cell frequency (P = 0.006). The secretions of IL-1β (P < 0.001), IL-6 (P < 0.001), IL-10 (P < 0.001), IFN-γ (P = 0.001) and TNF-α (P = 0.042) from PBMC were significantly increased with rhIL-21 stimulation. In summary, IL-21 has a causal role in the development of severe liver inflammation, which is upregulated in HB-ACLF and associated with severity of liver disease.
authors.affiliation: Hepatology Unit and Key Lab for Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.forename: S
authors.initials: S
authors.lastname: Ma
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: X
authors.initials: X
authors.lastname: Jiang
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: H
authors.initials: H
authors.lastname: Gao
authors.forename: M
authors.initials: M
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: W G H
authors.initials: WG
authors.lastname: Abbott
authors.forename: J
authors.initials: J
authors.lastname: Hou
mesh_terms: D000208:Acute Disease; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D058625:End Stage Liver Disease / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation; D000098546:Interleukin-21
chemical_list: D016207:Cytokines; D007378:Interleukins; D000098546:Interleukin-21