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Increased in vitro production and serum levels of the soluble lipopolysaccharide receptor sCD14 in liver disease
Ist Teil von
Journal of hepatology, 1995-10, Vol.23 (4), p.396-402
Ort / Verlag
Oxford: Elsevier B.V
Erscheinungsjahr
1995
Quelle
Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)
Beschreibungen/Notizen
Elevated concentrations of lipopolysaccharide have been found in serum of patients with severe parenchymal liver disease and its toxic effect is thought to be involved in hemodynamic disturbances seen in cirrhosis. 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 vitro production by lipopolysaccharide stimulated peripheral blood monocytes in patients with various liver diseases.
In acute viral hepatitis serum sCD14 levels were significantly higher during the first 2 weeks after onset of jaundice (n=11; 3.6±0.9 μg/ml (mean±SD)) than in healthy control individuals (n=52; 2.5±0.7 μg/ml;
p<0.001). These elevated serum levels corresponded to enhanced
in vitro production of sCD14 by lipopolysaccharide-stimulated peripheral blood monocytes (n=11; 365±262 ng/ml) as compared to control monocytes (n=52; 228±74 ng/ml;
p=0.02). Similarly, patients with alcoholic cirrhosis had significantly increased sCD14 serum levels (n=31; 4.5±3.2 μg/ml;
p<0.001) and
in vitro sCD14 production by lipopolysaccharide-stimulated monocytes (291±153 ng/ml;
p=0.014). Serum sCD14 levels correlated with the severity of disease (Child A: 2.6±1.0 μ/ml; Child B: 4.4±2.1 μ/ml; Child C: 7.8±5.1 μg/ml; Anova:
p=0.001). Patients with chronic viral hepatitis had only slightly elevated serum sCD14 levels (n=17; 2.9±0.7 μg/ml;
p=0.01) and increased
in vitro production of sCD14 by peripheral blood monocytes (320±128 ng/m;
p<0.001).
The elevated serum concentration of sCD14 in alcoholic cirrhosis and acute and chronic 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 cells to bind and respond to lipopolysaccharide. Elevated levels of sCD14 could in this way contribute to the toxic effects of lipopolysaccharide in severe liver disease.