Tumor-necrosis-factor and interleukin-6 response of peripheral blood monocytes to low concentrations of lipopolysaccharide in patients with alcoholic liver disease.

Plasma levels of endotoxin and tumor necrosis factor alpha (TNF alpha) and the cytokine response of isolated monocytes were examined in chronic alcohol abusers with various degrees of liver disease. In 35 patients - 19 with alcoholic fatty liver (AF), 7 with alcoholic hepatitis (AH), 9 with cirrhosis (AC) - and in 15 healthy controls (HC), plasma levels of endotoxin were measured in the limulus assay, and plasma TNF alpha in an immunoassay. The cytokine response of monocytes stimulated in vitro with low doses of endotoxin (range: 25 pg/ml to 2.5 ng/ml) was determined in a cytolytic TNF bioassay and in TNF alpha and interleukin-6 (IL-6) immunoassays. All patient groups had elevated plasma endotoxin levels, whereas plasma TNF alpha was elevated only in AC (43.1 +/- 15.2 vs. HC: 5.0 +/- 1.1 pg/ml). Monocytes from all patient groups released increased amounts of bioactive TNF: AF 5.39 +/- 1.70, AH 7.10 +/- 3.28, AC 2.44 +/- 0.54 vs. HC 1.21 +/- 0.30 ng/ml (stimulation with 2.5 ng/ml endotoxin over 3 hrs.). Similar results were obtained in the TNF alpha immunoassay. Increased release of IL-6 from monocytes was shown only for AF, while values in AC were comparable to those in HC. These data confirm that endotoxemia is frequent in chronic alcoholics. In concert with an increased cytokine response of the monocyte/macrophage system, endotoxemia might contribute to the pathogenesis of alcoholic liver disease.