Interleukin-10 gene down-expression in circulating mononuclear cells during infusion of drotrecogin-α activated: a pilot study

The purpose of this study was to investigate the gene expression of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) in circulating mononuclear cells harvested from septic shock patients on drotrecogin-α activated (DAA) in order to determine whether this treat...

Full description

Saved in:
Bibliographic Details
Published in:Critical care (London, England) England), 2010-01, Vol.14 (5), p.R163-R163
Main Authors: Lavaux, Thomas, Bilbault, Pascal, Launoy, Anne, Gaub, Marie-Pierre, Oudet, Pierre, Schneider, Francis
Format: Article
Language:English
Subjects:
Aged
Cohort Studies
Down-Regulation - drug effects
Down-Regulation - physiology
Gene Expression Regulation - drug effects
Humans
Infusions, Intravenous
Interleukin-10 - antagonists & inhibitors
Interleukin-10 - biosynthesis
Interleukin-10 - genetics
Leukocytes, Mononuclear - drug effects
Leukocytes, Mononuclear - metabolism
Leukocytes, Mononuclear - pathology
Middle Aged
Pilot Projects
Prospective Studies
Protein C - administration & dosage
Recombinant Proteins - administration & dosage
Shock, Septic - blood
Shock, Septic - drug therapy
Shock, Septic - pathology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The purpose of this study was to investigate the gene expression of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) in circulating mononuclear cells harvested from septic shock patients on drotrecogin-α activated (DAA) in order to determine whether this treatment has any effect on the inflammation phase. 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-α, IL-10 and IFN-γ mRNA expressions using the real-time quantitative polymerase chain reaction (RT-qPCR). Thirty-two septic shock patients were included: 16 with DAA at 24 μg/kg/h for 96 hours (DAA+) and 16 control (DAA-) eligible but contraindicated for DAA because of low platelet count. The basal characteristics were similar in both groups: mortality (50%), plasma cytokine concentrations, and baseline IFN-γ, TNF-α and IL-10 mRNA expressions (DAA+ vs. DAA-). At T2, there was a significant IFN-γ 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-γ (-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). 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-γ gene down-expression could represent markers of DAA response.
ISSN:1364-8535
1466-609X
DOI:10.1186/cc9252