Role of Interleukin-18 in Experimental Severe Acute Pancreatitis Complicated with Liver Injury

Background: Interleukin (IL)-18 is a newly discovered proinflammatory cytokine, whose serum level is closely associated with liver injury during severe acute pancreatitis (SAP), however, few studies have focused on its changes and significance in the impaired liver tissue. Aims: To investigate the expression of IL-18 in liver tissue of SAP rats and to appraise the role of IL-18 in liver injury during SAP. Methods: A rat model of SAP was induced by retrograde infusion of 4% sodium taurocholate into the biliary-pancreatic duct. Thirty-two rats were randomly divided into four groups: control group, SAP 6 h, SAP 12 h and SAP 18 h groups. The levels of serum amylase, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and amount of ascites were determined dynamically. The pancreatic and liver injuries were observed by light microscopy. The expression and distribution of precursor and mature IL-18 in liver tissue were measured by immunohistochemistry and Western blotting. Results: The levels of serum amylase, ALT, AST and amount of ascites increased significantly in the 6 h, 12 h and 18 h SAP groups, statistically higher than those in the controls (P0.01). These changes were paralleled with the histopathological changes of pancreatic and liver tissues. The intensive expression of IL-18 was located in the cytoplasm of Kupffer cells in liver tissue, and the number of positively stained Kupffer cells and expression of mature IL-18 increased significantly in the 6 h, 12 h and 18 h SAP groups when compared with those in the controls, especially in the 12 h group (P0.01). Conclusions: Kupffer cells are the main source of mature IL-18 in liver tissue. Overexpression of mature IL-18 may play a pivotal role in the pathogenesis of SAP complicated with liver injury.