Serum concentrations and peripheral secretion of the beta chemokines monocyte chemoattractant protein 1 and macrophage inflammatory protein 1alpha in alcoholic liver disease

Abstract

Background: Alcoholic liver disease is associated with increased hepatic expression of monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1alpha (MIP-1alpha).

Aims: 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.

Patients: 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.

Figure 1

Serum monocyte chemoattractant protein 1 (MCP-1) concentrations in patients with severe or mild to moderate alcoholic hepatitis, inactive alcoholic cirrhosis, and controls. Thick horizontal bars represent mean values. Concentrations in severe alcoholic cirrhosis were significantly higher than in cirrhotics or controls (p<0.01, Mann-Whitney U test).

Figure 2

Paired hepatic and peripheral vein (HV and PV) monocyte chemoattractant protein 1 (MCP-1) concentrations in patients with severe alcoholic hepatitis compared with mild to moderate hepatitis or cirrhosis.

Figure 3

Spontaneous peripheral blood mononuclear cell secretion of (A) monocyte chemoattractant protein 1 (MCP-1) and (B) macrophage inflammatory protein 1α (MIP-1α) in patients with severe alcoholic hepatitis and healthy controls. Thick horizontal bars represent mean values.

Figure 4

PBMC cytospin preparation hybridised with cDNA for macrophage inflammatory protein 1α (MIP-1α) chemokine mRNA (A, antisense probe; B, sense probe). Positive hybridisation is represented by dark granules, which are seen mostly in association with monocytes (M); lymphocytes (L) are mostly negative.