title: Interleukin-10 gene down-expression in circulating mononuclear cells during infusion of drotrecogin-α activated: a pilot study.
abstract: BACKGROUND
  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.
  
  
  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-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.
  
  
  RESULTS
  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).
  
  
  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-γ gene down-expression could represent markers of DAA response.
authors.affiliation: Department of Biochemistry and Molecular Biology, Hôpital de Hautepierre et Université de Strasbourg, Avenue Molière, 67098 Strasbourg, France. thomas.lavaux@chru-strasbourg.fr
authors.forename: Thomas
authors.initials: T
authors.lastname: Lavaux
authors.forename: Pascal
authors.initials: P
authors.lastname: Bilbault
authors.forename: Anne
authors.initials: A
authors.lastname: Launoy
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Gaub
authors.forename: Pierre
authors.initials: P
authors.lastname: Oudet
authors.forename: Francis
authors.initials: F
authors.lastname: Schneider
mesh_terms: D000368:Aged; D015331:Cohort Studies; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011486:Protein C / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012772:Shock, Septic / Q000097:blood* / Q000188:drug therapy / Q000473:pathology
chemical_list: D011486:Protein C; D011994:Recombinant Proteins; D016753:Interleukin-10; C421124:drotrecogin alfa activated
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