Increased monocyte MCP-1 production in acute alcoholic hepatitis

Monocyte chemoattractant protein-1 (MCP-1) is a potent mononuclear cell-specific chemotactic protein. MCP-1 is a candidate chemoattractant for activation and hepatic infiltration of mononuclear cells in alcoholic hepatitis (AH). Blood was collected from 15 patients with AH (mean bilirubin 17.6+/-3.5 mg/dl; normal 0. 2-1.0 mg/dl) on admission and at time points for up to 6 months. Peripheral blood monocytes were isolated and MCP-1 production assessed by measuring MCP-1 concentrations in monocyte culture supernatants after overnight (20 h) incubation. Monocytes from normal subjects did not product detectable MCP-1 unless stimulated with endotoxin (LPS;5 microg/ml). The mean level of constitutive MCP-1 from AH patient monocytes was 4694+/-2432 pg/ml 20 h on admission. The mean MCP-1 level for LPS-treated monocytes was 4903+/-1540 pg/ml 20 h for normal subjects and was significantly elevated in AH patients to 11589+/-3266 pg/ml/20 h. AH patient monocyte MCP-1 production was decreased in vitro when monocytes were treated with N-acetylcysteine (5 mM) and also decreased over the 6-month study as the patients improved clinically. MCP-1 plasma levels were below the detection limits of the assay used in both AH patients and normal subjects. Thus, monocytes from AH patients not only constitutively product MCP-1, but also produce higher levels of MCP-1 with endotoxin stimulation. Further studies are needed to clarify the role of MCP-1 in the activation and hepatic infiltration of mononuclear cells in alcoholic liver disease.