Tumour necrosis factor-alpha expression by activated monocytes and altered T-cell homeostasis in ascitic alcoholic cirrhosis: amelioration with norfloxacin

J Hepatol. 2004 Apr;40(4):624-31. doi: 10.1016/j.jhep.2003.12.010.


Background/aims: To investigate the distribution and activation state of circulating monocytes and T-cell subsets, their contribution to tumour necrosis factor-alpha (TNFalpha) production, and their potential relationship with bacterial products of enteric origin in alcoholic cirrhosis.

Methods: Peripheral blood monocytes and T-lymphocytes from 60 cirrhotic patients and 24 controls were characterized by four-color flow-cytometry after labelling of differentiation antigens and cytokines, before and after a 4-week course of norfloxacin or placebo.

Results: Monocytes from ascitic patients showed increased number, enhanced CD80 and HLA-DR surface levels, and spontaneous intracytoplasmic TNFalpha expression, when compared to non-ascitic patients and controls. Blood TNFalpha levels directly correlated with the amount of TNFalpha expressed by monocytes. In ascitic patients, there was a collapse of virgin CD4(+) and CD8(+) T-cell subsets; and, an expansion of activated CD4(+) T-cells. The above abnormalities were mainly restricted to ascitic patients with high serum levels of lypolysaccharide-binding-protein. Norfloxacin normalized the number of monocytes, reduced their activated phenotype and ability to produce TNFalpha and improved the abnormal T-cell homeostasis.

Conclusions: In ascitic cirrhosis with high lipolysaccharide-binding-protein, monocytes are spontaneously activated to produce TNFalpha and are major contributors to the elevated serum TNFalpha. The T-cell compartment is profoundly depleted. Enteric bacterial products play a relevant role in these immune cellular abnormalities.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins
  • Anti-Infective Agents / therapeutic use*
  • Ascites / drug therapy
  • Ascites / immunology
  • Carrier Proteins / blood
  • Case-Control Studies
  • Enterobacteriaceae / immunology
  • Enterobacteriaceae / pathogenicity
  • Female
  • Homeostasis
  • Humans
  • Immunity, Cellular
  • Lipopolysaccharides / blood
  • Liver Cirrhosis, Alcoholic / drug therapy*
  • Liver Cirrhosis, Alcoholic / immunology*
  • Liver Cirrhosis, Alcoholic / microbiology
  • Male
  • Membrane Glycoproteins / blood
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / immunology
  • Norfloxacin / therapeutic use*
  • Prospective Studies
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis*


  • Acute-Phase Proteins
  • Anti-Infective Agents
  • Carrier Proteins
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Tumor Necrosis Factor-alpha
  • lipopolysaccharide-binding protein
  • Norfloxacin