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01.03.2004 | Original

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

verfasst von: Pascal Bilbault, Thomas Lavaux, Abdeslam Lahlou, Béatrice Uring-Lambert, Marie-Pierre Gaub, Charline Ratomponirina, Nicolas Meyer, Pierre Oudet, Francis Schneider

Erschienen in: Intensive Care Medicine | Ausgabe 3/2004

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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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Titel: Transient Bcl-2 gene down-expression in circulating mononuclear cells of severe sepsis patients who died despite appropriate intensive care
verfasst von: Pascal Bilbault
Thomas Lavaux
Abdeslam Lahlou
Béatrice Uring-Lambert
Marie-Pierre Gaub
Charline Ratomponirina
Nicolas Meyer
Pierre Oudet
Francis Schneider
Publikationsdatum: 01.03.2004
Verlag: Springer-Verlag
Erschienen in: Intensive Care Medicine / Ausgabe 3/2004
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-003-2118-z

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