Role of defective monocyte interleukin‐10 release in tumor necrosis factor‐alpha overproduction in alcoholic cirrhosis (original) (raw)

Abstract

Monocytes of patients with alcoholic cirrhosis produce higher amounts of tumor necrosis factor-alpha (TNF-a) after Hpopolysaccharide (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 pg/mL [40 to 500] v 513 pg/mL [152 to 1,335]; P = .008) contrasting with increased TNF-er 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-e~ 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/mL; 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. (HEPATOLOGY 1995;22:1436-1439.) 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. 1' 2 Immunostaining for TNF-a is increased in the liver during alcoholic hepatitis, 3 and patients with either stable alcoholic cirrhosis or alcoholic hepatitis have

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