Influence of drotrecogin alpha (activated) infusion on the variation of Bax/Bcl-2 and Bax/Bcl-xl ratios in circulating mononuclear cells: a cohort study in septic shock patients.
Fiche publication
Date publication
janvier 2007
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MEYER Nicolas, Pr OUDET Pierre
Tous les auteurs :
Bilbault P, Lavaux T, Launoy A, Gaub MP, Meyer N, Oudet P, Pottecher T, Jaeger A, Schneider F
Lien Pubmed
Résumé
OBJECTIVE: Drotrecogin alpha (activated) (DAA), or recombinant human activated protein C, is a new treatment in sepsis-induced multiple organ failure, leading to significant reduction in the mortality rate, thanks to its anticoagulant properties. It has been suggested that DAA has anti-inflammatory and antiapoptotic effects in sepsis animal models. This study investigates the potential actions of DAA on circulating mononuclear cells apoptosis in human septic shock. DESIGN: Prospective, cohort study. SETTING: Two intensive care wards and two research laboratories in a university hospital. PATIENTS: Twenty-two septic shock patients with DAA treatment (DAA+), 19 septic shock patients without DAA treatment (DAA-), and 14 healthy controls were successively enrolled, but only 20 DAA+ and 16 DAA- patients fulfilled criteria for statistical analysis. INTERVENTIONS: Blood samples were collected at inclusion and 24 hrs later. MEASUREMENTS AND MAIN RESULTS: Circulating mononuclear cell apoptosis levels were assessed by flow cytometry with annexin V, and variations of the apoptotic rheostats (Bax/Bcl-2 and Bax/Bcl-xl ratios) were analyzed by real-time reverse transcription-polymerase chain reaction. Apoptosis was significantly increased in septic shock patients (DAA+, 12 +/- 6.4%; DAA-, 10.4 +/- 5%) vs. healthy patients (3.4 +/- 2.1%, p < .001). Twenty-four hours after DAA infusion, apoptosis was significantly lower in the DAA+ group compared with DAA- ones (respectively, 11.7 +/- 5.3% and 16.2 +/- 7.6%, p < .001). At inclusion, DAA+ and DAA- groups showed comparable Bax/Bcl-2 ratio (DAA+, 0.92 +/- 0.9; DAA-, 1.32 +/- 0.87) and Bax/Bcl-xl ratio (DAA+, 2 +/- 1.04; DAA-, 1.31 +/- 0.93). In contrast, 24 hrs later we observed a significant decrease in these ratios, indicating an antiapoptotic effect in the DAA+ group (Bax/Bcl-2, 0.39 +/- 0.27; Bax/Bcl-xl, 0.68 +/- 0.35) compared with the DAA- group (Bax/Bcl-2, 1.81 +/- 1.1; Bax/Bcl-xl, 1.22 +/- 0.92, p = .001 and p = .039, respectively). CONCLUSIONS: In vivo, in human septic shock, DAA has antiapoptotic effects on circulating mononuclear cells, assessed by a significant decrease of both the Bax/Bcl-2 and Bax/Bcl-xl ratios.
Référence
Crit Care Med. 2007 Jan;35(1):69-75.