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

Hepatology. 1995 Nov;22(5):1436-9.

Abstract

Monocytes of patients with alcoholic cirrhosis produce higher amounts of tumor necrosis factor-alpha (TNF-alpha) after lipopolysaccharide (LPS) stimulation. The mechanisms of the overproduction remain undefined. IL-10 (IL-10) is an antiinflammatory cytokine known to downregulate TNF-alpha secretion by monocytes. The present study analyzes IL-10 production by monocytes and its control on TNF-alpha secretion in alcoholic cirrhosis. LPS-stimulated monocytes from alcoholic cirrhotics (n = 13) showed decreased IL-10 (median, 240 pg/mL [40 to 500] upsilon 513 pg/mL [152 to 1,335]; 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-alpha secretion. On the other hand, preincubation with anti-IL-10 monoclonal antibodies led to significant increase in TNF-alpha 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-alpha 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 characteristics TNF-alpha overproduction observed in this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cells, Cultured
  • Female
  • Humans
  • Interleukin-10 / metabolism*
  • Interleukin-10 / pharmacology
  • Liver Cirrhosis, Alcoholic / blood
  • Liver Cirrhosis, Alcoholic / metabolism*
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • Recombinant Proteins / pharmacology
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10