Interleukin-1 receptor antagonist expression is inversely associated with outcomes of hepatitis B-related acute-on-chronic liver failure

摘要

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-1 beta 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-1 beta 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.