HMGB1 mediates acute liver injury in sepsis through pyroptosis of liver macrophages

Sepsis is a systemic inflammatory response syndrome caused by infection. Septic patients often show an acute liver dysfunction during the onset of sepsis in ICU. We found the levels of ALT, AST, TBIL increased significantly in septic patients and returned after recovery from sepsis in our ICU (P<0.05), and had a similar trend for HMGB1. To explore the role of hepatic macrophage in acute liver injury, we simulated the process of acute liver injury by cecal ligation and puncture (CLP) in mice. We assessed the inflammatory infiltration of the liver by HE, and examined the levels of ALT and AST in serum and the expression of HMGB1, IL-1 beta in the serum and the relative expression of mRNA in the liver at the different time of CLP model. Also we found the rate of pyroptosis cells in liver was about 18.19%, while 16.29% in macrophages by Flow cytometry. So our study has demonstrated that HMGB1 may promote the pyroptosis of liver macrophages to mediate acute liver injury in sepsis.