CHEMOKINE AND CELL-ADHESION MOLECULE MESSENGER-RNA EXPRESSION AND NEUTROPHIL INFILTRATION IN LIPOPOLYSACCHARIDE-INDUCED HEPATITIS IN ETHANOL-FED RATS

Neutrophil infiltration is a feature of alcoholic hepatitis (AH), and although the mechanism by which this occurs is unclear, it may involve a chemotactic gradient. We used lipopolysaccharide (LPS) to induce, i n ethanol-fed rats, liver damage similar to that seen in AH. To our kn owledge, this study is the first to examine the effect of ethanol on L PS-stimulated chemokine mRNA expression in this model. Hepatic cytokin e-induced neutrophil chemoattractant (CINC)-1, CINC-2, monocyte chemoa ttractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1 b eta, MIP-2, and eotaxin mRNA levels were elevated 1 to 3 hr post-LPS i n both groups. Maximal expression of MIP-2 and MCP-1 mRNA was higher i n ethanol-fed rats 1 hr post-LPS, whereas CINC-2 mRNA expression was e levated above controls at 12 to 24 hr. Hepatic intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 mRNA levels were elev ated in both groups at 1 hr, whereas L-selectin expression in ethanol- fed rats was elevated above controls at 12 to 24 hr. Hepatic neutrophi l infiltration was highest during maximal hepatocyte necrosis. These d ata suggest that cell adhesion molecules, in conjunction with elevated cytokines and the subsequently induced chemokines, may assist in the formation of a chemotactic gradient within the liver, causing the neut rophil infiltration seen both in this model and possibly in AH.