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Chronic Alcohol Consumption Is Associated With an Increased Cytotoxic Profile of Circulating Lymphocytes That May Be Related With the Development of Liver Injury

Authors

  • Francisco Javier Laso,

    1. From the Unidad de Alcoholismo (FJL, ET, MM), Servicio de Medicina Interna II, Hospital Universitario de Salamanca; Departamento de Medicina (FJL, JA, AO), Universidad de Salamanca; Servicio de Citometría and Centro de Investigación del Cáncer (IBMCC; CSIC and Universidad de Salamanca) (JA, JMV, AO), Salamanca, Spain.
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  • Julia Almeida,

    1. From the Unidad de Alcoholismo (FJL, ET, MM), Servicio de Medicina Interna II, Hospital Universitario de Salamanca; Departamento de Medicina (FJL, JA, AO), Universidad de Salamanca; Servicio de Citometría and Centro de Investigación del Cáncer (IBMCC; CSIC and Universidad de Salamanca) (JA, JMV, AO), Salamanca, Spain.
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  • Emiliano Torres,

    1. From the Unidad de Alcoholismo (FJL, ET, MM), Servicio de Medicina Interna II, Hospital Universitario de Salamanca; Departamento de Medicina (FJL, JA, AO), Universidad de Salamanca; Servicio de Citometría and Centro de Investigación del Cáncer (IBMCC; CSIC and Universidad de Salamanca) (JA, JMV, AO), Salamanca, Spain.
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  • José Miguel Vaquero,

    1. From the Unidad de Alcoholismo (FJL, ET, MM), Servicio de Medicina Interna II, Hospital Universitario de Salamanca; Departamento de Medicina (FJL, JA, AO), Universidad de Salamanca; Servicio de Citometría and Centro de Investigación del Cáncer (IBMCC; CSIC and Universidad de Salamanca) (JA, JMV, AO), Salamanca, Spain.
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  • Miguel Marcos,

    1. From the Unidad de Alcoholismo (FJL, ET, MM), Servicio de Medicina Interna II, Hospital Universitario de Salamanca; Departamento de Medicina (FJL, JA, AO), Universidad de Salamanca; Servicio de Citometría and Centro de Investigación del Cáncer (IBMCC; CSIC and Universidad de Salamanca) (JA, JMV, AO), Salamanca, Spain.
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  • Alberto Orfao

    1. From the Unidad de Alcoholismo (FJL, ET, MM), Servicio de Medicina Interna II, Hospital Universitario de Salamanca; Departamento de Medicina (FJL, JA, AO), Universidad de Salamanca; Servicio de Citometría and Centro de Investigación del Cáncer (IBMCC; CSIC and Universidad de Salamanca) (JA, JMV, AO), Salamanca, Spain.
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Reprint requests: Francisco Javier Laso, Servicio de Medicina Interna II, Hospital Universitario, Paseo de San Vicente 58-182, 37007 Salamanca, Spain; Fax: +34-923294739; E-mail: laso@usal.es

Abstract

Background:  Apoptosis has recently emerged as a key component of acute and chronic liver diseases and it could be related to alcoholic liver disease. In the present study, we attempted to analyze the cytotoxic profile of circulating lymphocytes in chronic alcoholic patients grouped according to ethanol intake status and presence of liver disease.

Methods:  We investigate the phenotypic and functional behavior of different compartments of peripheral blood (PB) cytotoxic T and natural killer (NK) cells in chronic alcoholic patients without liver disease and active ethanol intake (AWLD group; n = 22), and in subjects with alcohol liver cirrhosis (ALC group; n = 22).

Results:  AWLD patients showed an expansion of both CD4+/CD8+ cytotoxic T cells and NK/T cells, in association with an enhanced cytolytic activity against K562 cells and a higher ability to induce in vitro expression of the pro-apoptotic protein APO2.7 in HepG2 cells. Conversely, ethanol intake in ALC patients was associated with decreased NK cell numbers, a reduced cytotoxic activity against K562 cells without significant changes in the expression of APO2.7, and a pro-fibrotic profile of cytokine secretion.

Conclusions:  Overall, our results suggest that alcoholic patients display different phenotypical and functional changes in circulating PB cytotoxic lymphocytes according to the presence of alcoholic liver disease, which could be related to the development and progress of liver injury.

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