INCREASED IN-VITRO PRODUCTION AND SERUM LEVELS OF THE SOLUBLE LIPOPOLYSACCHARIDE RECEPTOR SCD14 IN LIVER-DISEASE

Elevated concentrations of lipopolysaccharide have been found in serum of patients with severe parenchymal liver disease and its toxic effec t is thought to be involved in hemodynamic disturbances seen in cirrho sis, A soluble form of the receptor (sCD14) for lipopolysaccharide is present in serum and is released by stimulated macrophages, indicating macrophage activation, We investigated sCD14 serum levels and in vitr o production by lipopolysaccharide stimulated peripheral blood monocyt es in patients with various liver diseases. In acute viral hepatitis s erum sCD14 levels were significantly higher during the first 2 weeks a fter onset of jaundice (n=11; 3.6+/-0.9 mu ml (mean+/-SD)) than in hea lthy control individuals (n=52; 2.5+/-0.7 mu g/ml; p<0.001). These ele vated serum levels corresponded to enhanced in vitro production of sCD 14 by lipopolysaccharide-stimulated peripheral blood monocytes (n=11; 365+/-262 ng/ml) as compared to control monocytes (n=52; 228+/-74 ng/m l; p=0.02). Similarly, patients with alcoholic cirrhosis had significa ntly increased sCD14 serum levels (n=31; 4.5+/-3.2 mu g/ml; p<0.001) a nd in vitro sCD14 production by lipopolysaccharide-stimulated monocyte s (291+/-153 ng/ml; p=0.014). Serum sCD14 levels correlated with the s everity of disease (Child A: 2.6+/-1.0 mu g/ml; Child B: 4.4+/-2.1 mu g/ml; Child C: 7.8+/-5.1 mu g/ml; Anova: p=0.001). Patients with chron ic viral hepatitis had only slightly elevated serum sCD14 levels (n=17 ; 2.9/-0.7 mu g/ml; p=0.01) and increased in vitro production of sCD14 by peripheral blood monocytes (320+/-128 ngl mi; p<0.001). The elevat ed serum concentration of sCD14 in alcoholic cirrhosis and acute and c hronic viral hepatitis points to an increased macrophage activation in these diseases. sCD14 from serum is able to associate with cells not expressing membrane CD14, such as endothelial cells, allowing those ce lls to bind and respond to lipopolysaccharide. Elevated levels of sCD1 4 could in this way contribute to the toxic effects of lipopolysacchar ide in severe liver disease.