Effect of Acute and Chronic Alcohol Administration to Rats on the Expression of Interleukin‐6 Cell‐Surface Receptors of Hepatic Parenchymal and Nonparenchymal Cells

Rats were treated with alcohol either acutely (continuous, 7‐hr intravenous infusion; blood alcohol levels ∼35 mM) or chronically (liquid diet, 12–14 weeks). Three hr before killing, the animals received Gram‐negative bacterial lipopolysaccharide (LPS) or saline. Hepatocytes, Kupffer cells, and liver sinusoidal endothelial cells were isolated by liver collagenase perfusion and centrifugal elutriation, and used for measurements of recombinant human [ 125 I]interleukin‐6 binding. Dissociation constant ( K d ) and the amount of cell‐surface receptors ( B max ) were measured on whole cells, at 4°C. Two binding sites were detected on all three cell types: high‐affinity ( K d 1 , from 20 to 125 PM) and low‐affinity ( K d 2 , from 0.2 to 2 nM), with low B max ( B max from 0.4 to 12 fmol/10 6 cells) and high B max ( B max2 , from 10 to 210 fmol/10 6 cells). Hepatocytes displayed an 8‐fold higher binding capacity for high‐affinity sites ( B max1 ) than the other two cell types. Acute ethanol treatment induced the following significant changes in the binding parameters: a decrease in K d 1 for hepatocytes and Kupffer cells, an increase in B max2 for hepatocytes, and a decrease in B max1 for Kupffer cells. Although the control (nonalcoholic) liquid diet per se completely suppressed the high‐affinity binding sites, alcohol‐containing diet induced only one change: a significant increase in K d 2 for hepatocytes. No changes in the binding parameters were seen after LPS administration to the chronically treated group. In the acute group, LPS mimicked alcohol action on hepatocyte binding parameters. Alcohol blunted LPS effects. No changes were observed in the cytokine binding to Kupffer cells after LPS injection. The results show that alcohol alters interleukin‐6 cell‐surface receptor properties and receptor amount on hepatocytes and Kupffer cells. By demonstrating the presence of interleukin‐6 receptors on non‐parenchymal liver cells, our data also suggest that these cells may be involved in an autocrine loop‐like response, which could be a target for alcohol action on the liver.