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

被引:115
作者
Albillos, A
de la Hera, A
Reyes, E
Monserrat, J
Muñoz, L
Nieto, M
Prieto, A
Sanz, E
Alvarez-Mon, M
机构
[1] Univ Alcala de Henares, CSIC,Ctr Nacl Biotechnol, Lab Enfermedades Sistema Inmune & Oncol, Fac Med,Dept Med,Unidad I&D Asociada, Alcala De Henares 28871, Madrid, Spain
[2] Univ Madrid, Hosp Ramon y Cajal, Serv Gastroenterol, Madrid 3, Spain
[3] Univ Madrid, Hosp Principe Asturias, Serv Enfermedades Sistema Inmune & Oncol, Madrid 3, Spain
关键词
alcoholic cirrhosis; cytotoxic T cells; helper T cells; lypolysaccharide; lypolysaccharide binding protein; mononuclear cells;
D O I
10.1016/j.jhep.2003.12.010
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:624 / 631
页数:8
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