Interleukin-1 receptor antagonist expression is inversely associated with outcomes of hepatitis B-related acute-on-chronic liver failure
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- Published online on: April 19, 2017 https://doi.org/10.3892/etm.2017.4361
- Pages: 2867-2875
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Copyright: © Lai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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Abstract
Interleukin-1 receptor antagonist (IL-1ra) is a naturally occurring anti-inflammatory antagonist of the proinflammatory cytokine IL-1, a critical factor in many inflammatory diseases. The aim of the present study was to investigate the role of IL‑1ra in hepatitis B‑related acute‑on‑chronic liver failure (HB‑ACLF). Serum cytokine concentrations were measured using a Q‑Plex array in 31 patients with HB‑ACLF, 28 patients with acute hepatitis B (AHB), 31 patients with chronic hepatitis B (CHB) and 15 healthy control patients (HCs). Additionally, peripheral blood mononuclear cells (PBMCs) from patients with HB‑ACLF were incubated with PBS or lipopolysaccharide and/or different concentrations of recombinant human IL‑1ra (rhIL‑1ra) in vitro. Cytokines in the supernatant were measured using a Q‑Plex array. The median serum IL‑1ra level in patients with HB‑ACLF was 186.46 (350.22) pg/ml, which was significantly higher than all other groups (AHB, P=0.012; CHB, P<0.001; HCs, P<0.001). However, the ratio of IL‑1ra/IL‑1β was significantly lower in the HB‑ACLF group compared with the AHB group (P=0.048). Median serum IL‑1ra levels in patients with AHB were also significantly increased compared with those in the CHB (P<0.001) and HC (P<0.001) groups. Patients who succumbed to mortality within 3 months of the study were found to have significantly lower IL‑1ra concentrations (P=0.02) and IL‑1ra/IL‑1β ratios (P=0.007) compared with surviving patients with HB‑ACLF. Furthermore, serum IL‑1ra concentrations were negatively associated with the Model for End‑stage Liver Disease score (r=‑0.870; P<0.001). Cytokine secretion by PBMCs in vitro was significantly inhibited in a dose‑dependent manner by rhIL‑1ra (125‑500 ng/ml; all P<0.05). These results suggest that IL‑1ra is associated with the development of liver inflammation, which is reduced in patients with HB‑ACLF and inversely associated with disease severity.