Excessive in vitro bacterial lipopolysaccharide-induced production of monokines in cirrhosis



The objective of this study was to analyze monokine production by peripheral blood mononuclear cells from patients with alcoholic cirrhosis. The capacity of peripheral blood mononuclear cells and purified monocytes from these patients to produce tumor necrosis factor α, interleukin 1β, and interleukin 6 was investigated. Spontaneous production of tumor necrosis factor α, interleukin 6 and interleukin 1β was similar in cirrhotic and healthy subjects, but serum levels of interleukin 6 (<2 U/ml vs. 9.5 ± 3 U/ml) and tumor necrosis factor α (3.1 ± 1.2 pg/ml vs. 12.0 ± 1.2 pg/ml) were significantly higher in cirrhotic patients. However, peripheral blood mononuclear cells or purified monocytes from patients with alcoholic liver cirrhosis, stimulated in vitro with Escherichia coli lipopolysaccharide, displayed a marked increase of tumor necrosis factor α, interleukin 1β and interleukin 6 secretions compared with healthy controls. A striking feature of this overproduction was its reversibility as assessed by allowing cells to rest in vitro without lipopolysaccharide for 1 to 7 days before stimulation. In such conditions, tumor necrosis factor α and interleukin 6 secretions declined to levels present in healthy subjects in whom production remained stable, whereas interleukin 1β secretion markedly decreased in both groups to the point where no difference could be seen. This reversible oversecretion of cytokines after lipopolysaccharide stimulation, along with the lack of abnormality of spontaneous cytokine secretion, suggests that monocytes in these patients may have undergone an in vivo activation process analogous to a priming phenomenon. The in vitro activation with lipopolysaccharide may represent the correlate of in vivo endotoxemia observed during acute events such as sepsis. This might lead-possibly through the recognized cytopathic and cytotoxic effects of excessive production of monokines-to the decompensation of the underlying liver disease. Monokine oversecretion may also play a role in the pathogenesis and perpetuation of the disease and may be associated with clinical and biological features of cirrhosis such as cachexia, muscle wasting and hypergammaglobulinemia.(HEPATOLOGY 1990; 11:628:634.)