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Published in: Intensive Care Medicine 3/2008

01-03-2008 | Brief Report

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

Authors: Martijn D. de Kruif, Lucienne C. Lemaire, Ida A. Giebelen, Joachim Struck, Nils G. Morgenthaler, Jana Papassotiriou, Peter J. Elliott, Tom van der Poll

Published in: Intensive Care Medicine | Issue 3/2008

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Abstract

Objective

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.

Subjects

Thirty-two healthy male volunteers.

Interventions

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.

Conclusions

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.
Literature
1.
go back to reference 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 166:1197–1205CrossRefPubMed 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 166:1197–1205CrossRefPubMed
2.
go back to reference 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:R816–824CrossRefPubMed 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:R816–824CrossRefPubMed
3.
go back to reference 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:R37–45CrossRefPubMed 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:R37–45CrossRefPubMed
4.
go back to reference 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 28:219–226CrossRefPubMed 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 28:219–226CrossRefPubMed
5.
go back to reference Morgenthaler NG, Struck J, Alonso C, Bergmann A (2005) Measurement of midregional proadrenomedullin in plasma with an immunoluminometric assay. Clin Chem 51:1823–1829CrossRefPubMed Morgenthaler NG, Struck J, Alonso C, Bergmann A (2005) Measurement of midregional proadrenomedullin in plasma with an immunoluminometric assay. Clin Chem 51:1823–1829CrossRefPubMed
6.
go back to reference Morgenthaler NG, Struck J, Thomas B, Bergmann A (2004) Immunoluminometric assay for the midregion of pro-atrial natriuretic peptide in human plasma. Clin Chem 50:234–236CrossRefPubMed Morgenthaler NG, Struck J, Thomas B, Bergmann A (2004) Immunoluminometric assay for the midregion of pro-atrial natriuretic peptide in human plasma. Clin Chem 50:234–236CrossRefPubMed
7.
go back to reference 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 52:112–119CrossRefPubMed 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 52:112–119CrossRefPubMed
8.
go back to reference 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 34:1996–2003CrossRefPubMed 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 34:1996–2003CrossRefPubMed
9.
go back to reference 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 184:373–376CrossRefPubMed 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 184:373–376CrossRefPubMed
10.
go back to reference 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 363:600–607CrossRefPubMed 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 363:600–607CrossRefPubMed
11.
go back to reference 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 141:47–56PubMed 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 141:47–56PubMed
12.
go back to reference 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 178:1845–1851PubMed 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 178:1845–1851PubMed
13.
go back to reference Lowry SF (2005) Human endotoxemia: a model for mechanistic insight and therapeutic targeting. Shock 24(Suppl 1):94–100CrossRefPubMed Lowry SF (2005) Human endotoxemia: a model for mechanistic insight and therapeutic targeting. Shock 24(Suppl 1):94–100CrossRefPubMed
14.
go back to reference Morgenthaler NG, Struck J, Fischer-Schulz C, Bergmann A (2002) Sensitive immunoluminometric assay for the detection of procalcitonin. Clin Chem 48:788–790PubMed Morgenthaler NG, Struck J, Fischer-Schulz C, Bergmann A (2002) Sensitive immunoluminometric assay for the detection of procalcitonin. Clin Chem 48:788–790PubMed
15.
go back to reference 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 52:827–831CrossRefPubMed 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 52:827–831CrossRefPubMed
16.
go back to reference Nguyen HB, Smith D (2007) Sepsis in the 21st century: recent definitions and therapeutic advances. Am J Emerg Med 25:564–571CrossRefPubMed Nguyen HB, Smith D (2007) Sepsis in the 21st century: recent definitions and therapeutic advances. Am J Emerg Med 25:564–571CrossRefPubMed
17.
go back to reference 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 35:1012–1018CrossRefPubMed 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 35:1012–1018CrossRefPubMed
18.
go back to reference Laan RF, Jansen TL, van Riel PL (1999) Glucocorticosteroids in the management of rheumatoid arthritis. Rheumatology (Oxford) 38:6–12CrossRef Laan RF, Jansen TL, van Riel PL (1999) Glucocorticosteroids in the management of rheumatoid arthritis. Rheumatology (Oxford) 38:6–12CrossRef
19.
go back to reference 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 27:265–268CrossRefPubMed 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 27:265–268CrossRefPubMed
20.
go back to reference 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 18:207–212CrossRefPubMed 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 18:207–212CrossRefPubMed
Metadata
Title
The influence of corticosteroids on the release of novel biomarkers in human endotoxemia
Authors
Martijn D. de Kruif
Lucienne C. Lemaire
Ida A. Giebelen
Joachim Struck
Nils G. Morgenthaler
Jana Papassotiriou
Peter J. Elliott
Tom van der Poll
Publication date
01-03-2008
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 3/2008
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-007-0955-x

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