Background and aims
Primary biliary cholangitis (PBC) is a slowly progressive cholestatic, autoimmune liver disease, which leads to fibrosis, cirrhosis and liver failure. PBC is characterized by the presence of specific serum antimitochondrial (AMA) and antinuclear (ANA) antibodies. Oxidative stress plays an important role in the pathogenesis of chronic liver diseases. The serum level of 8-isoprostane, a product of lipid peroxidation, is a marker of oxidative stress in vivo. Oxidative stress caused production of interleukin 8 (IL-8), which belongs to pro-inflammatory cytokines. In that way it can cause the recruitment of inflammatory cells and induces a further increase in oxidant stress mediators.
The aim of the present study was to determine whether the degree of lipid peroxidation determined by measuring the serum level of 8-isoprostane influences the progression of PBC. We also evaluated the serum concentration of IL-8 , and studied the correlation between the level of IL-8, 8-isoprostane and specific autoantibodies.
Methods
In the study, 72 PBC patients, 15 pathological controls (patients with other autoimmune liver diseases), and 15 healthy blood donors were enrolled. AMAs and ANAs, Il-8 and 8-isoprostane were detected using commercially-available ELISA kits.
Results
Elevated levels of IL-8 were detected in 58% of patients with PBC. They were significantly higher compared with the control groups: 91.1 ± 20.1 vs. 4.8 ± 0.6 pg/mL, p = 0.0077. In AMA-positive and ANA-positive PBC groups we found that 70% of patients had a higher concentration of IL-8. Serum 8-isoprostane was also significantly elevated in PBC (238.9 [3.8–500.0] pg/mL), in comparison to healthy controls (12.3 [1.6–22.1] pg/mL, p < 0.001). Serum 8-isoprostane values were positively correlated with a higher concentration of IL-8, total cholesterol, bilirubin concentration and severe liver fibrosis (determined by liver biopsy). 8-Isoprostane concentration was not significantly associated to sex, age and biochemical data. Type III procollagen peptide (PIIINP), a serum marker of hepatic fibrogenesis was increased in PBC patients compare to healthy group (p<0.001). Serum 8-isoprostane correlated positively also with PIIINP.
Conclusions
The results show that IL-8 may be an important factor in liver pathologies in patients with PBC, especially in the development of inflammatory processes. A correlation between the concentration of IL-8, 8-isoprostatne and specific autoantibodies was observed. Furthermore, oxidative stress caused by increased lipid peroxidation was determined to be involved in the pathogenesis of PBC. Remarkably, the obtained results indicate that serum 8-isoprostane might be a promising marker for prediction of the degree of liver fibrosis.
