TUMOR-NECROSIS-FACTOR AND INTERLEUKIN-6 RESPONSE OF PERIPHERAL-BLOOD MONOCYTES TO LOW CONCENTRATIONS OF LIPOPOLYSACCHARIDE IN PATIENTS WITHALCOHOLIC LIVER-DISEASE

Plasma levels of endotoxin and tumor necrosis factor alpha (TNF alpha) and the cytokine response of isolated monocytes were examined in chro nic alcohol abusers with various degrees of liver disease. In 35 patie nts - 19 with alcoholic fatty liver (AF), 7 with alcoholic hepatitis ( AH), 9 with cirrhosis (AC)- and in 15 healthy controls (HC), plasma le vels of endotoxin were measured in the limulus assay, and plasma TNF a lpha 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) wa s determined in a cytolytic TNF bioassay and in TNF alpha and interleu kin-6 (IL-6) immunoassays. All patient groups had elevated plasma endo toxin 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. Ho 1.21 +/- 0.30 ng/ml (stimulation wi th 2.5 ng/ml endotoxin over 3 hrs.). Similar results were obtained in the TNF alpha immunoassay. Increased release of IL-6 from monocytes wa s shown only for AF, while values in AC were comparable to those in HC . These data confirm that endotoxemia is frequent in chronic alcoholic s. In concert with an increased cytokine response of the monocyte/macr ophage system, endotoxemia might contribute to the pathogenesis of alc oholic liver disease.