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Transient Bcl-2 gene down-expression in circulating mononuclear cells of severe sepsis patients who died despite appropriate intensive care

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Abstract

Objective

To assess the levels of expression of the antiapoptotic gene Bcl-2 and the proapoptotic gene Bax in circulating mononuclear cells (CMNC) harvested during the course of severe sepsis (SS) in formerly non-immunocompromised patients undergoing hospital-acquired infection, in parallel to cytokine levels.

Design

Prospective study.

Setting

Intensive care unit.

Participants

A total of 24 patients without immunodeficiency undergoing standard goal-directed therapy for nosocomial SS, 10 critically ill patients without sepsis, and 10 healthy controls.

Interventions

Blood was collected before infection and within 12 h, 1, 3 and 7 days after fever onset, to determine plasma concentrations of IL-6, IL-10, TNF-alpha, C-reactive protein, whole blood cell counts, lymphocyte subsets, annexin V labelling for apoptosis, and Bax and Bcl-2 relative RNA expression by real-time polymerase chain reaction.

Results

SS patients displayed increased cytokine concentrations, TNF-alpha being significantly increased at full-blown sepsis. Within 12 h after onset of infection, lymphocyte counts were lower in SS patients than in critically ill controls (p=0.001), and this phenomenon was marked in CD4+ and CD8+ subsets (p<0.001). This was associated with enhanced apoptosis in CMNC (15.7±8.7% vs 3.4±2.1%, p<0.001) and a significant down-expression of the Bcl-2 gene throughout the study (p<0.05). In contrast, the expression of Bax did not change significantly. Within 12 h of fever onset, non-survivors expressed a 10-fold down-expression of Bcl-2 when compared to survivors (p<0.001).

Conclusions

An early transient down-expression of the gene Bcl-2 occurred in CMNC harvested from SS patients who died despite intensive care. In contrast, the expression of the gene Bax did not change significantly.

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Authors and Affiliations

  1. Services de Réanimation Médicale, Hôpital de Hautepierre, Avenue Molière, 67098, Strasbourg, France

    Pascal Bilbault & Francis Schneider

  2. Services de Biochimie et de Biologie Moléculaire, Hôpitaux Universitaires et Faculté de Médecine de l’Université L. Pasteur, Strasbourg, France

    Thomas Lavaux, Marie-Pierre Gaub, Charline Ratomponirina & Pierre Oudet

  3. Services d’Immunologie et d’Hématologie, Hôpitaux Universitaires et Faculté de Médecine de l’Université L. Pasteur, Strasbourg, France

    Abdeslam Lahlou & Béatrice Uring-Lambert

  4. Département de stastitiques, Hôpitaux Universitaires et Faculté de Médecine de l’Université L. Pasteur, Strasbourg, France

    Nicolas Meyer

Authors
  1. Pascal Bilbault
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  2. Thomas Lavaux
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  3. Abdeslam Lahlou
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  7. Nicolas Meyer
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  9. Francis Schneider
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Corresponding author

Correspondence to Francis Schneider.

Additional information

This work was supported by the Délégation à la Recherche Clinique des Hôpitaux Universitaires de Strasbourg (PHRC Régional 2001-Grant 2629).

Pascal Bilbault and Thomas Lavaux contributed equally to this study.

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Bilbault, P., Lavaux, T., Lahlou, A. et al. Transient Bcl-2 gene down-expression in circulating mononuclear cells of severe sepsis patients who died despite appropriate intensive care. Intensive Care Med 30, 408–415 (2004). https://doi.org/10.1007/s00134-003-2118-z

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  • DOI: https://doi.org/10.1007/s00134-003-2118-z

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