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Different changes in mitochondrial apoptotic pathway in lymphocytes and granulocytes in cirrhotic patients with sepsis

Authors

  • Vincenza Precone,

    1. Department of Internal and Specialistic Medicine, Infectious Diseases and Viral Hepatitis Unit, Second University of Naples, Naples, Italy
    2. CEINGE-Biotecnologie Avanzate, Naples, Italy
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  • Gianfranca Stornaiuolo,

    1. Department of Internal and Specialistic Medicine, Infectious Diseases and Viral Hepatitis Unit, Second University of Naples, Naples, Italy
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  • Annamaria Amato,

    1. Department of Internal and Specialistic Medicine, Infectious Diseases and Viral Hepatitis Unit, Second University of Naples, Naples, Italy
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  • Giuseppina Brancaccio,

    1. Department of Internal and Specialistic Medicine, Infectious Diseases and Viral Hepatitis Unit, Second University of Naples, Naples, Italy
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  • Salvatore Nardiello,

    1. Department of Internal and Specialistic Medicine, Infectious Diseases and Viral Hepatitis Unit, Second University of Naples, Naples, Italy
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  • Giovanni B. Gaeta

    Corresponding author
    • Department of Internal and Specialistic Medicine, Infectious Diseases and Viral Hepatitis Unit, Second University of Naples, Naples, Italy
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Correspondence

Prof. Giovanni B. Gaeta, Chair of Infectious Diseases, Second University of Naples, Policlinico, Via S. Pansini 5, Bld. 3, Naples 80131, Italy

Tel: +39 081 5666223

Fax: +39 081 5666744

e-mail: giovannib.gaeta@unina2.it

Abstract

Background & Aims

Apoptosis regulates leucocyte response during bacterial infections. This study explored leucocyte apoptotic pathway in cirrhotic patients with or without infections or sepsis.

Methods

In cirrhotic patients with bacterial infection or sepsis, the expression of Caspase 9, Bcl-2 family proteins, which comprises pro-apoptotic molecules, such as Bax, and anti-apoptotic molecules, such as Bcl-2 and Bcl-xL, were measured in peripheral lymphocytes and granulocytes. Regulatory microRNAs MIR-15 and MIR-16 were also measured.

Results

This study enrolled 80 patients with cirrhosis, of whom 28 had no evidence of infections, 32 had bacterial infections and 20 had sepsis; reference values were obtained from 10 age-matched healthy subjects. An over-expression of Caspase-9 and pro-apoptotic protein Bax was found in lymphocytes of cirrhotic patients with infection or sepsis as compared with non-infected cases (P = 0.05 and 0.0001, respectively), while anti-apoptotic proteins Bcl-2 and Bcl-xL were downregulated. In granulocytes, lowest expression of pro-apoptotic protein Bax occurred in septic patients, while in cirrhotics with infections anti-apoptotic Bcl-2 and Bcl-xL were upregulated. Eight patients died; the survivors had less derangements in Bax, Bcl-2 and BcL-xL expression than non-survivors. The pro-apoptotic miRNA, MIR-15 and MIR-16, were upregulated in cirrhotics with bacterial infections.

Conclusions

Overall, the data show in lymphocytes, and not in granulocytes, an activation of the pro-apoptotic pathway in cirrhotic patients with bacterial infections, which correlates with the severity of the infection and the outcome.

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