This work was supported by the National Health and Medical Research Council of Australia and The University of Queensland. H.L.P. is the recipient of an Australian Postgraduate Award.
Chemokine and Cell Adhesion Molecule mRNA Expression and Neutrophil Infiltration in Lipopolysaccharide-Induced Hepatitis in Ethanol-Fed Rats
Article first published online: 30 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 22, Issue 8, pages 1713–1718, November 1998
How to Cite
Pennington, H. L., Wilce, P. A. and Worrall, S. (1998), Chemokine and Cell Adhesion Molecule mRNA Expression and Neutrophil Infiltration in Lipopolysaccharide-Induced Hepatitis in Ethanol-Fed Rats. Alcoholism: Clinical and Experimental Research, 22: 1713–1718. doi: 10.1111/j.1530-0277.1998.tb03970.x
- Issue published online: 30 MAY 2006
- Article first published online: 30 MAY 2006
- Received for publication May 8, 1998; accepted July 27, 1998
- Adhesion Molecule
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, in ethanol-fed rats, liver damage similar to that seen in AH. To our knowledge, this study is the first to examine the effect of ethanol on LPS-stimulated chemokine mRNA expression in this model. Hepatic cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, monocyte chemoattractant protein-1 (MCP-l), macrophage inflammatory protein (MIP)-1 β, MIP-2, and eotaxin mRNA levels were elevated 1 to 3 hr post-LPS in both groups. Maximal expression of MIP-2 and MCP-1 mRNA was higher in ethanol-fed rats 1 hr post-LPS, whereas CINC-2 mRNA expression was elevated above controls at 12 to 24 hr. Hepatic intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 mRNA levels were elevated in both groups at 1 hr, whereas L-selectin expression in ethanol-fed rats was elevated above controls at 12 to 24 hr. Hepatic neutrophil infiltration was highest during maximal hepatocyte necrosis. These data 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 neutrophil infiltration seen both in this model and possibly in AH.