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

2004, Journal of Hepatology

To investigate the distribution and activation state of circulating monocytes and T-cell subsets, their contribution to tumour necrosis factor-alpha (TNFα) production, and their potential relationship with bacterial products of enteric origin in alcoholic cirrhosis.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.Monocytes from ascitic patients showed increased number, enhanced CD80 and HLA-DR surface levels, and spontaneous intracytoplasmic TNFα expression, when compared to non-ascitic patients and controls. Blood TNFα levels directly correlated with the amount of TNFα 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 TNFα and improved the abnormal T-cell homeostasis.In ascitic cirrhosis with high lipolysaccharide-binding-protein, monocytes are spontaneously activated to produce TNFα and are major contributors to the elevated serum TNFα. The T-cell compartment is profoundly depleted. Enteric bacterial products play a relevant role in these immune cellular abnormalities.