Serum concentrations and peripheral secretion of the beta chemokines monocyte chemoattractant protein 1 and macrophage inflammatory protein 1alpha in alcoholic liver disease.
BACKGROUND
Alcoholic liver disease is associated with increased hepatic expression of monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1alpha (MIP-1alpha).


OBJECTIVE
To determine whether concentrations of chemokines in the peripheral circulation reflect disease activity, and whether chemokine secretion is restricted to the liver or is part of a systemic inflammatory response in alcoholic liver disease.


METHODS
Fifty one patients with alcoholic liver disease and 12 healthy controls.


METHODS
Peripheral vein (and hepatic vein in patients undergoing transjugular liver biopsy) chemokine concentrations were measured by ELISA. Chemokine secretion and transcription in isolated peripheral mononuclear cells were assessed using ELISA and in situ hybridisation in patients with severe alcoholic hepatitis.


RESULTS
Serum MCP-1 concentrations were higher in alcoholic hepatitis compared with cirrhosis or healthy controls. MIP-1alpha concentrations were below the assay sensitivity in most patients. Serum MCP-1 concentrations correlated significantly with serum aspartate aminotransferase and creatinine. In severe alcoholic hepatitis, MCP-1 concentrations were higher in hepatic compared with peripheral veins; in mild alcoholic hepatitis there was no difference. Mononuclear cell secretion of both MCP-1 and MIP-1alpha was higher in severe alcoholic hepatitis compared with healthy controls, and chemokine mRNA was identified in monocytes.


CONCLUSIONS
Serum MCP-1 concentrations are raised in alcoholic liver disease and reflect severity of hepatic inflammation. Monocyte secretion of both MCP-1 and MIP-1alpha is increased in severe alcoholic hepatitis. Both intrahepatic sources and peripheral mononuclear cells contribute to the raised serum MCP-1 concentrations.
Fisher
N C
NC
Liver Research Laboratories, MRC Centre for Immune Regulation, Institute of Clinical Science, Queen Elizabeth Medical Centre, Birmingham B15 2TH, UK.
Neil
D A
DA
Williams
A
A
Adams
D H
DH
D015415:Biomarkers / Q000097:blood; D018929:Cell Culture Techniques; D018932:Chemokine CCL2 / Q000097:blood*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D004797:Enzyme-Linked Immunosorbent Assay; D006503:Hepatic Veins / Q000378:metabolism; D006519:Hepatitis, Alcoholic / Q000097:blood; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood; D008108:Liver Diseases, Alcoholic / Q000097:blood*; D019402:Macrophage Inflammatory Proteins / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
D015415:Biomarkers; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger