Monocytes of patients with alcoholic cirrhosis pro
duce higher amounts of tumor necrosis factor-alpha (me) after lipopolysaccharide (LPS) stimulation. The mechanisms of this overproduction remain undefined. IL-10 (IL-10) is an antiinflammatory cytokine known to downregulate TNF-a secretion by monocytes. The present study analyzes IL-10 production by monocytes and its control on TNF-a secretion in alcoholic cirrhosis. LPS-stimulated monocytes from alcoholic cirrhotics (n = 13) showed decreased IL-10 (median, 240 p g / d [40 to 5001 u 513 p g / d [152 to 1,3351; P = .008) contrasting with increased TNF-a secretion (18,120 pg/mL [2,500 to 46,2001 u 8,100 p g / d [4,400 to 14,5801; P = .01) compared with controls (n = 13). Cells from cirrhotic patients were normally responsive to recombinant IL-10, which induced a dose dependent decrease of TNF-a secretion. On the other hand, preincubation with anti-IL-10 monoclonal antibodies led to significant increase in TNF-a secretion in controls (median, 7,325 to 16,800 pg/& P = .002) but not in cells from cirrhotic patients (16,535 to 20,450 pg/ mL; P = .14), abolishing the difference in TNF-a production between cirrhotic patients and controls. It is concluded that defective IL-10 secretion by monocytes from alcoholic cirrhotic patients could be involved in the characteristic TNF-a overproduction observed in this disease. (€IEPATOLOGY 1995;221436-1439.)
Peripheral blood monocytes from patients with alcoholic cirrhosis or hepatitis produce higher amounts of tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6) after lipopolysaccharide (LPS) stimulation.''2 Immunostaining for TNF-a is increased in the liver during alcoholic he pa ti ti^,^ and patients with either stable alcoholic cirrhosis or alcoholic hepatitis have