Intensive Care Medicine

, Volume 34, Issue 8, pp 1371–1376 | Cite as

Gene profiling in human blood leucocytes during recovery from septic shock

  • Didier Payen
  • Anne-Claire Lukaszewicz
  • Ioulia Belikova
  • Valérie Faivre
  • Catherine Gelin
  • Stefan Russwurm
  • Jean-Marie Launay
  • Nicolas Sevenet



To assess blood leucocytes gene profiling during recovery phase of septic shock; to test the relation between encoding gene expression and protein level.

Study design

Gene expression levels were studied at days 0, 1, 7 and 28 (D0, 1, 7 and 28) on a dedicated microarray of 340 genes involved in inflammatory processes.


16-bed intensive care unit, Lariboisière University hospital.


Seventeen septic shock patients enrolled when at least one additional organ dysfunction occurred.

Measurements and results

Changes over time were compared with D0 via the ratio Dx/D0. The time-related gene expression study showed significant changes in ten genes. Among them, S100A8 and S100A12 had a reduced expression over time compared with D0, whereas CD74's expression increased. The microarray results were validated by RT-qPCR for four genes. The S100A8 plasma levels decrease along recovery in parallel with the gene expression decrease. The CD74 gene expression evolution significantly correlated with HLA-DR monocyte expression.


These results are the first description of variations in expression of key inflammatory genes in the course of the septic shock recovery period.


Microarray Kinetic of gene expression CD 74 S100A gene and protein HLA-DR expression 



This work was supported in part by “Programme Hospitalier Recherche Clinique (PHRC) AORO2006” and by “Quadrienal plan for research from the French Ministry of Research” EA 322.

Supplementary material

134_2008_1048_MOESM1_ESM.doc (388 kb)
Electronic Supplementary Material (DOC 388K)


  1. 1.
    Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D (2006) Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 34:344–353PubMedCrossRefGoogle Scholar
  2. 2.
    Boldrick JC, Alizadeh AA, Diehn M, Dudoit S, Liu CL, Belcher CE, Botstein D, Staudt LM, Brown PO, Relman DA (2002) Stereotyped and specific gene expression programs in human innate immune responses to bacteria. Proc Natl Acad Sci USA 99:972–977PubMedCrossRefGoogle Scholar
  3. 3.
    Chinnaiyan AM, Huber-Lang M, Kumar-Sinha C, Barrette TR, Shankar-Sinha S, Sarma VJ, Padgaonkar VA, Ward PA (2001) Molecular signatures of sepsis: multiorgan gene expression profiles of systemic inflammation. Am J Pathol 159:1199–1209PubMedGoogle Scholar
  4. 4.
    Prucha M, Ruryk A, Boriss H, Moller E, Zazula R, Herold I, Claus RA, Reinhart KA, Deigner P, Russwurm S (2004) Expression profiling: toward an application in sepsis diagnostics. Shock 22:29–33PubMedCrossRefGoogle Scholar
  5. 5.
    Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699–709PubMedCrossRefGoogle Scholar
  6. 6.
    Abraham E, Wunderink R, Silverman H, Perl TM, Nasraway S, Levy H, Bone R, Wenzel RP, Balk R, Allred RP et al. (1995) Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb Sepsis Study Group. J Am Med Assoc 273:934–941CrossRefGoogle Scholar
  7. 7.
    Fisher CJ Jr, Dhainaut JF, Opal SM, Pribble JP, Balk RA, Slotman GJ, Iberti TJ, Rackow EC, Shapiro MJ, Greenman RL et al. (1994) Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. J Am Med Assoc 271:1836–1843CrossRefGoogle Scholar
  8. 8.
    Rice TW, Wheeler AP, Morris PE, Paz HL, Russell JA, Edens TR, Bernard GR (2006) Safety and efficacy of affinity-purified, anti-tumor necrosis factor-alpha, ovine fab for injection (CytoFab) in severe sepsis. Crit Care Med 34:2271–2281PubMedCrossRefGoogle Scholar
  9. 9.
    Calvano SE, Xiao W, Richards DR, Felciano RM, Baker HV, Cho RJ, Chen RO, Brownstein BH, Cobb JP, Tschoeke SK, Miller-Graziano C, Moldawer LL, Mindrinos MN, Davis RW, Tompkins RG, Lowry SF (2005) A network-based analysis of systemic inflammation in humans. Nature 437:1032–1037PubMedCrossRefGoogle Scholar
  10. 10.
    Pachot A, Lepape A, Vey S, Bienvenu J, Mougin B, Monneret G (2006) Systemic transcriptional analysis in survivor and non-survivor septic shock patients: a preliminary study. Immunol Lett 106:63–71PubMedCrossRefGoogle Scholar
  11. 11.
    Bone RC, Sibbald WJ, Sprung CL (1992) The ACCP-SCCM consensus conference on sepsis and organ failure. Chest 101:1481–1483PubMedCrossRefGoogle Scholar
  12. 12.
    Calvano SE, Greenlee PG, Reid AM, deRiesthal HF, Shires GT, Antonacci AC (1988) Granulocyte contamination of Ficoll-Hypaque preparations of mononuclear cells following thermal injury may lead to substantial overestimation of lymphocyte recovery. J Trauma 28:353–361PubMedCrossRefGoogle Scholar
  13. 13.
    Ikemoto M, Tanaka T, Takai Y, Murayama H, Tanaka K, Fujita M (2003) New ELISA system for myeloid-related protein complex (MRP8/14) and its clinical significance as a sensitive marker for inflammatory responses associated with transplant rejection. Clin Chem 49:594–600PubMedCrossRefGoogle Scholar
  14. 14.
    Pachot A, Monneret G, Brion A, Venet F, Bohe J, Bienvenu J, Mougin B, Lepape A (2005) Messenger RNA expression of major histocompatibility complex class II genes in whole blood from septic shock patients. Crit Care Med 33:31–38, 236–237PubMedCrossRefGoogle Scholar
  15. 15.
    Roth J, Vogl T, Sorg C, Sunderkotter C (2003) Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules. Trends Immunol 24:155–158PubMedCrossRefGoogle Scholar
  16. 16.
    Matza D, Kerem A, Shachar I (2003) Invariant chain, a chain of command. Trends Immunol 24:264–268PubMedCrossRefGoogle Scholar
  17. 17.
    Monneret G, Finck ME, Venet F, Debard AL, Bohe J, Bienvenu J, Lepape A (2004) The anti-inflammatory response dominates after septic shock: association of low monocyte HLA-DR expression and high interleukin-10 concentration. Immunol Lett 95:193–198PubMedCrossRefGoogle Scholar
  18. 18.
    Caille V, Chiche JD, Nciri N, Berton C, Gibot S, Boval B, Payen D, Mira JP, Mebazaa A (2004) Histocompatibility leukocyte antigen-D related expression is specifically altered and predicts mortality in septic shock but not in other causes of shock. Shock 22:521–526PubMedCrossRefGoogle Scholar
  19. 19.
    Kerkhoff C, Klempt M, Sorg C (1998) Novel insights into structure and function of MRP8 (S100A8) and MRP14 (S100A9). Biochim Biophys Acta 1448:200–211PubMedCrossRefGoogle Scholar
  20. 20.
    PasseyRJ,XuK,HumeDA,GeczyCL (1999) S100A8: emerging functions and regulation. J Leukoc Biol 66:549–556PubMedGoogle Scholar
  21. 21.
    RavasiT,HsuK,GoyetteJ,SchroderK, Yang Z, Rahimi F, Miranda LP, Alewood PF, Hume DA, Geczy C (2004) Probing the S100 protein family through genomic and functional analysis. Genomics 84:10–22PubMedCrossRefGoogle Scholar
  22. 22.
    Koike T, Harada N, Yoshida T, Morikawa M (1992) Regulation of myeloid-specific calcium binding protein synthesis by cytosolic protein kinase C. J Biochem (Tokyo) 112:624–630Google Scholar
  23. 23.
    Vandal K, Rouleau P, Boivin A, Ryckman C, Talbot M, Tessier PA (2003) Blockade of S100A8 and S100A9 suppresses neutrophil migration in response to lipopolysaccharide. J Immunol 171:2602–2609PubMedGoogle Scholar
  24. 24.
    Hsu K, Passey RJ, Endoh Y, Rahimi F, Youssef P, Yen T, Geczy CL (2005) Regulation of S100A8 by glucocorticoids. J Immunol 174:2318–2326PubMedGoogle Scholar
  25. 25.
    Vogl T, Tenbrock K, Ludwig S, Leukert N, Ehrhardt C, van Zoelen MA, Nacken W, Foell D, van der Poll T, Sorg C, Roth J (2007) Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat Med 13:1042–1049PubMedCrossRefGoogle Scholar
  26. 26.
    Viemann D, Barczyk K, Vogl T, Fischer U, Sunderkotter C, Schulze-Osthoff K, Roth J (2007) MRP8/MRP14 impairs endothelial integrity and induces a caspase-dependent and -independent cell death program. Blood 109:2453–2460CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Didier Payen
    • 1
  • Anne-Claire Lukaszewicz
    • 1
  • Ioulia Belikova
    • 1
  • Valérie Faivre
    • 1
  • Catherine Gelin
    • 3
  • Stefan Russwurm
    • 4
  • Jean-Marie Launay
    • 2
  • Nicolas Sevenet
    • 2
  1. 1.Lariboisière University Hospital, Assistance Publique – Hôpitaux de Paris, Department of Anesthesiology and Critical Care MedicineUniversité Paris 7 René DiderotParisFrance
  2. 2.Biochemistry LaboratoryLariboisière University HospitalParisFrance
  3. 3.INSERM U662Saint Louis HospitalParisFrance
  4. 4.SIRS-LabJenaGermany

Personalised recommendations