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.