Up-Regulation of Interleukin 33 and Soluble ST2 Serum Levels in Liver Failure

Abstract

IL-33, a member of the IL-1 family, induces the production of pro-inflammatory and Th2-associated cytokines and may also serve as an 'alarmin' similar to HMGB1. Soluble ST2 has been implicated as a decoy receptor, to attenuate Th2 inflammatory responses. The relevance of both molecules in hepatic failure is unknown. The trial was a prospective preliminary study in a university hospital surgical ICU; 11 patients with acute liver failure (ALF) and 12 patients with acute-on-chronic liver failure (ACLF), who were admitted to the ICU; 14 patients with chronic hepatic failure (CHF) awaiting liver transplantation; 13 healthy individuals served as controls. IL-33 and soluble ST2 concentrations were determined by enzyme linked immunosorbent assay (ELISA). The concentration of IL-33 and soluble ST2 was significantly higher in ALF, ACLF, and CHF patients compared with the controls. Soluble ST2 serum concentration was significantly elevated in ALF and ACLF compared with CHF; moreover, soluble ST2 was significantly higher in CHF compared with healthy controls. IL-33 and soluble ST2 serum levels correlated significantly (r = 0.6117, P < 0.0001). Moreover, there was a correlation between IL-33 serum levels and alanine aminotransferase (ALT) activity in CHF, ALF, and ACLF patients (r = 0.4321, P = 0.0171). Our data provide evidence for elevated levels of IL-33 and soluble ST2 in liver failure, which could a sign of immune hyperactivation, and/or a mechanism to down-regulate inflammation. Especially, soluble ST2 maybe useful to discern acute from chronic hepatic failure or to monitor the course and the severity of the disease.