Cytoprotection by interleukin-6 against liver injury induced by lipopolysaccharide

The role of interleukin (IL)-6 in inflammatory injury remains controversial. The present study elucidated the role of IL-6 in liver damage during severe inflammation induced by intraperitoneal administration of lipopolysaccharide (LPS; 1 mg/kg) using IL-6 null (-/-) mice and corresponding wild-type (WT) mice. Histological study showed that LPS treatment caused more severe liver injury with centrilobular vacuolation of hepatocytes and neutrophilic infiltration in the liver of IL-6 (-/-) mice; in contrast, neutrophilic infiltration and mild vacuolar change of hepatocytes were found in the liver of LPS-treated WT mice. Protein levels of proinflammatory molecules, such as IL-1beta, macrophage inflammatory protein-1alpha, and macrophage chemoattractant protein-1, in the livers were significantly greater in IL-6 (-/-) mice than in WT mice after LPS challenge. These results directly indicate that IL-6 is protective against liver injury induced by bacterial endotoxin, at least partly, via the modulation of proinflammatory cytokines and chemokines.