Serum inflammatory cytokines, complement components, and soluble interleukin 2 receptor in primary biliary cirrhosis

Abstract

Primary biliary cirrhosis (PBC) is a chronic cholestatic autoimmune liver disease characterized by selective destruction of the intrahepatic bile ducts and highly specific serum anti-mitochondrial autoantibodies (AMA). Several studies have attempted to determine the cytokine pattern characterizing PBC, yet no definitive data have been gathered. The present study was designed to evaluate pro-inflammatory cytokines (IL-1beta, IL-6, TNFalpha), soluble IL-2 receptor (sIL-2R, e.g. soluble CD25), and complement components (C1q, C3, factor B, properdin) levels in sera from 84 patients with PBC and 41 controls. PBC was characterized by significantly higher levels of all pro-inflammatory cytokines when compared to controls; these included IL-1beta (433.3 +/- 13.2 vs. 316.6 +/- 14.7 pg/ml, P < 0.001), IL-6 (701 +/- 17.4 vs. 158 +/- 22.5 pg/ml, P < 0.001), TNFalpha (3.38 +/- 0.6 pg/ml vs. undetectable, P = 0.001), and sIL-2R (1527.1 +/- 106 vs. 566.4 +/- 28.7 U/ml, P < 0.001). Similarly, all complement components were also significantly higher in PBC compared to control sera. In conclusion, PBC sera manifest higher levels of sIL-2R and complement components and this may reflect a perpetuated immune activation. As expected, we also report that all major pro-inflammatory cytokine levels are enhanced in PBC. Further longitudinal analyses could demonstrate a correlation between these markers and disease stage or inflammatory activity, to predict histological staging, disease activity, and response to treatment.