Role of defective monocyte interleukin-10 release in tumor necrosis factor-alpha overproduction in alcoholic cirrhosis



Monocytes of patients with alcoholic cirrhosis produce higher amounts of tumor necrosis factor-alpha (TNF-α) after lipopolysaccharide (LPS) stimulation. The mechanisms of this overproduction remain undefined. IL-10 (IL-10) is an antiinflammatory cytokine known to downregulate TNF-α secretion by monocytes. The present study analyzes IL-10 production by monocytes and its control on TNF-α secretion in alcoholic cirrhosis. LPS-stimulated monocytes from alcoholic cirrhotics (n = 13) showed decreased IL-10 (median, 240 pg/mL [40 to 500] v 513 pg/mL [152 to 1,335]; P = .008) contrasting with increased TNF-α secretion (18,120 pg/mL [2,500 to 46,200] v 8,100 pg/mL [4,400 to 14,580]; 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-α secretion. On the other hand, preincubation with anti-IL-10 monoclonal antibodies led to significant increase in TNF-α secretion in controls (median, 7,325 to 16,800 pg/mL; P = .002) but not in cells from cirrhotic patients (18,535 to 20,450 pg/mL; P = .14), abolishing the difference in TNF-α 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-α overproduction observed in this disease. (Hepatology 1995; 22:1436–1439).