Interleukin-10 gene down-expression in circulating mononuclear cells during infusion of drotrecogin-alpha activated: a pilot study.
Fiche publication
Date publication
janvier 2010
Auteurs
Membres identifiés du Cancéropôle Est :
Pr OUDET Pierre
Tous les auteurs :
Lavaux T, Bilbault P, Launoy A, Gaub MP, Oudet P, Schneider F
Lien Pubmed
Résumé
INTRODUCTION: The purpose of this study was to investigate the gene expression of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in circulating mononuclear cells harvested from septic shock patients on drotrecogin-alpha activated (DAA) in order to determine whether this treatment has any effect on the inflammation phase. METHODS: We conducted a prospective cohort study in two intensive care departments. Blood samples were collected at inclusion (T1) and 36 hours later (T2) to measure plasma cytokines and the changes in intracellular TNF-alpha, IL-10 and IFN-gamma mRNA expressions using the real-time quantitative polymerase chain reaction (RT-qPCR). Thirty-two septic shock patients were included: 16 with DAA at 24 mug/kg/h for 96 hours (DAA+) and 16 control (DAA-) eligible but contraindicated for DAA because of low platelet count. RESULTS: The basal characteristics were similar in both groups: mortality (50%), plasma cytokine concentrations, and baseline IFN-gamma, TNF-alpha and IL-10 mRNA expressions (DAA+ vs. DAA-). At T2, there was a significant IFN-gamma gene down-regulation in DAA+ but not in DAA- patients (-0.34 (-0.62; +1.54) vs. +1.41 (+0.35; +5.87), P = 0.008). In survivors, DAA administration was associated with a down-expression of both IFN-gamma (-0.65 (-0.93; 0.48) vs. +0.7 (-0.04; +1.26), P = 0.01) and IL-10 (-0.78 (-0.92; -0.6) vs. -0.18 (-0.68; +0.46), P = 0.038). In the non-survivors, DAA infusion was associated with IL-10 over-expression when compared with survivors (+0.54 (-0.35; +11.52) vs. -0.78 (-0.92; -0.6), P < 0.001). CONCLUSIONS: In this study, lack of IL-10 gene down-expression despite a 36-hour infusion of DAA is an ominous sign in septic shock patients suggesting that DAA is not able to reverse the outcome. Our results suggest that DAA can decrease the expression of anti-inflammatory cytokines in septic shock patients. IL-10 or IFN-gamma gene down-expression could represent markers of DAA response.
Référence
Crit Care. 2010;14(5):R163