Tumour necrosis factor-alpha expression by activated monocytes and altered T-cell homeostasis in ascitic alcoholic cirrhosis: amelioration with norfloxacin.
OBJECTIVE
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.
Albillos
Agustín
A
Laboratorio de Enfermedades del Sistema Inmune y Oncología, Unidad I+D Asociada al Centro Nacional de Biotecnología, Departamento de Medicina, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain. aalbillosm@meditex.es
Hera Ad
Antonio de la
Ade L
Reyes
Eduardo
E
Monserrat
Jorge
J
Muñoz
Leticia
L
Nieto
Mónica
M
Prieto
Alfredo
A
Sanz
Eva
E
Alvarez-Mon
Melchor
M
D000209:Acute-Phase Proteins; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001201:Ascites / Q000188:drug therapy / Q000276:immunology; D002352:Carrier Proteins / Q000097:blood; D016022:Case-Control Studies; D004755:Enterobacteriaceae / Q000276:immunology / Q000472:pathogenicity; D005260:Female; D006706:Homeostasis; D006801:Humans; D007111:Immunity, Cellular; D008070:Lipopolysaccharides / Q000097:blood; D008104:Liver Cirrhosis, Alcoholic / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009643:Norfloxacin / Q000627:therapeutic use*; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D000890:Anti-Infective Agents; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009643:Norfloxacin; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein