Intensive Care Medicine

, Volume 34, Issue 3, pp 518–522 | Cite as

The influence of corticosteroids on the release of novel biomarkers in human endotoxemia

  • Martijn D. de KruifEmail author
  • Lucienne C. Lemaire
  • Ida A. Giebelen
  • Joachim Struck
  • Nils G. Morgenthaler
  • Jana Papassotiriou
  • Peter J. Elliott
  • Tom van der Poll
Brief Report



Sepsis intervention studies need better patient stratification methods, and one way to realize this is the introduction of stable biomarkers. A set of recently developed novel biomarkers, based upon precursor-fragments of short-lived hormones, was previously shown to be increased during sepsis. However, it is not known whether these biomarkers are influenced by sepsis intervention strategies. Therefore we investigated the markers in a model of human endotoxemia intervened by increasing doses of prednisolone.

Design and setting

Prospective, open-label study in a specialized clinical research unit of a university hospital.


Thirty-two healthy male volunteers.


Subjects received prednisolone orally at doses of 0, 3, 10 or 30 mg (n = 8 per group) at 2 h before intravenous injection of Escherichia coli lipopolysaccharide (LPS) (4 ng/kg). Blood samples were drawn during 24 h after LPS injection.

Measurements and results

LPS injection caused an increase in levels of midregional pro-adrenomedullin (MR-proADM), midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-arginine–vasopressin (CT-proAVP) and procalcitonin (PCT). Prednisolone caused a dose dependent inhibition of MR-proADM, MR-proANP and CT-proAVP levels.


These results show that a set of novel, highly stable sepsis biomarkers was increased during human endotoxemia and was dose-dependently inhibited by corticosteroid pre-treatment.


Corticosteroids Biological markers Endotoxin Sepsis 



We thank Johanna Hetzel, Angelina Herzberg, Barbara Schäffus and Anne Schmiedel for excellent technical assistance. We thank the Department of Clinical Epidemiology and Biostatistics, AMC, for support in the statistical analysis.

Open Access

This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.


  1. 1.
    Eichacker PQ, Parent C, Kalil A, Esposito C, Cui X, Banks SM, Gerstenberger EP, Fitz Y, Danner RL, Natanson C (2002) Risk and the efficacy of antiinflammatory agents: retrospective and confirmatory studies of sepsis. Am J Respir Crit Care Med 166:1197–1205CrossRefPubMedGoogle Scholar
  2. 2.
    Christ-Crain M, Morgenthaler NG, Struck J, Harbarth S, Bergmann A, Muller B (2005) Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study. Crit Care 9:R816–824CrossRefPubMedGoogle Scholar
  3. 3.
    Morgenthaler NG, Struck J, Christ-Crain M, Bergmann A, Muller B (2005) Pro-atrial natriuretic peptide is a prognostic marker in sepsis, similar to the APACHE II score: an observational study. Crit Care 9:R37–45CrossRefPubMedGoogle Scholar
  4. 4.
    Morgenthaler NG, Muller B, Struck J, Bergmann A, Redl H, Christ-Crain M (2007) Copeptin, a stable peptide of the arginine vasopressin precursor, is elevated in hemorrhagic and septic shock. Shock 28:219–226CrossRefPubMedGoogle Scholar
  5. 5.
    Morgenthaler NG, Struck J, Alonso C, Bergmann A (2005) Measurement of midregional proadrenomedullin in plasma with an immunoluminometric assay. Clin Chem 51:1823–1829CrossRefPubMedGoogle Scholar
  6. 6.
    Morgenthaler NG, Struck J, Thomas B, Bergmann A (2004) Immunoluminometric assay for the midregion of pro-atrial natriuretic peptide in human plasma. Clin Chem 50:234–236CrossRefPubMedGoogle Scholar
  7. 7.
    Morgenthaler NG, Struck J, Alonso C, Bergmann A (2006) Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin Chem 52:112–119CrossRefPubMedGoogle Scholar
  8. 8.
    Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret GY (2006) Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Crit Care Med 34:1996–2003CrossRefPubMedGoogle Scholar
  9. 9.
    Preas HL 2nd, Nylen ES, Snider RH, Becker KL, White JC, Agosti JM, Suffredini AF (2001) Effects of anti-inflammatory agents on serum levels of calcitonin precursors during human experimental endotoxemia. J Infect Dis 184:373–376CrossRefPubMedGoogle Scholar
  10. 10.
    Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Muller B (2004) Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet 363:600–607CrossRefPubMedGoogle Scholar
  11. 11.
    Minneci PC, Deans KJ, Banks SM, Eichacker PQ, Natanson C (2004) Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose. Ann Intern Med 141:47–56PubMedGoogle Scholar
  12. 12.
    de Kruif MD, Lemaire LC, Giebelen IA, van Zoelen MA, Pater JM, van den Pangaart PS, Groot AP, de Vos AF, Elliott PJ, Meijers JC, Levi M, van der Poll T (2007) Prednisolone dose-dependently influences inflammation and coagulation during human endotoxemia. J Immunol 178:1845–1851PubMedGoogle Scholar
  13. 13.
    Lowry SF (2005) Human endotoxemia: a model for mechanistic insight and therapeutic targeting. Shock 24(Suppl 1):94–100CrossRefPubMedGoogle Scholar
  14. 14.
    Morgenthaler NG, Struck J, Fischer-Schulz C, Bergmann A (2002) Sensitive immunoluminometric assay for the detection of procalcitonin. Clin Chem 48:788–790PubMedGoogle Scholar
  15. 15.
    Gegenhuber A, Struck J, Poelz W, Pacher R, Morgenthaler NG, Bergmann A, Haltmayer M, Mueller T (2006) Midregional pro-A-type natriuretic peptide measurements for diagnosis of acute destabilized heart failure in short-of-breath patients: comparison with B-type natriuretic peptide (BNP) and amino-terminal proBNP. Clin Chem 52:827–831CrossRefPubMedGoogle Scholar
  16. 16.
    Nguyen HB, Smith D (2007) Sepsis in the 21st century: recent definitions and therapeutic advances. Am J Emerg Med 25:564–571CrossRefPubMedGoogle Scholar
  17. 17.
    Lipiner-Friedman D, Sprung CL, Laterre PF, Weiss Y, Goodman SV, Vogeser M, Briegel J, Keh D, Singer M, Moreno R, Bellissant E, Annane D (2007) Adrenal function in sepsis: the retrospective Corticus cohort study. Crit Care Med 35:1012–1018CrossRefPubMedGoogle Scholar
  18. 18.
    Laan RF, Jansen TL, van Riel PL (1999) Glucocorticosteroids in the management of rheumatoid arthritis. Rheumatology (Oxford) 38:6–12CrossRefGoogle Scholar
  19. 19.
    Lee-Wong M, McClelland S, Chong K, Fernandez E (2006) A case of hydrocortisone desensitization in a patient with radiocontrast-induced anaphylactoid reaction and corticosteroid allergy. Allergy Asthma Proc 27:265–268CrossRefPubMedGoogle Scholar
  20. 20.
    Cunnington D, Smith N, Steed K, Rosengarten P, Kelly AM, Teichtahl H (2005) Oral versus intravenous corticosteroids in adults hospitalised with acute asthma. Pulm Pharmacol Ther 18:207–212CrossRefPubMedGoogle Scholar

Copyright information

© The Author(s) 2007

Authors and Affiliations

  • Martijn D. de Kruif
    • 1
    Email author
  • Lucienne C. Lemaire
    • 2
  • Ida A. Giebelen
    • 1
    • 3
  • Joachim Struck
    • 4
  • Nils G. Morgenthaler
    • 4
  • Jana Papassotiriou
    • 4
  • Peter J. Elliott
    • 5
    • 6
  • Tom van der Poll
    • 1
    • 3
  1. 1.Center for Experimental and Molecular Medicine, Room G2-132Academic Medical CenterAmsterdamThe Netherlands
  2. 2.Department of AnesthesiologyUniversity Medical Center UtrechtUtrechtThe Netherlands
  3. 3.Center for Infection and Immunity AmsterdamAcademic Medical Center, University of AmsterdamAmsterdamThe Netherlands
  4. 4.Research DepartmentBrahms AGHennigsdorf/BerlinGermany
  5. 5.CombinatoRx, Inc.CambridgeUSA
  6. 6.Sirtris PharmaceuticalsCambridgeUSA

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