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

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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.

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Acknowledgements

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.

Author information

Authors and Affiliations

  1. Center for Experimental and Molecular Medicine, Room G2-132, Academic Medical Center, Meibergdreef 9, 1105, Amsterdam, AZ, The Netherlands

    Martijn D. de Kruif, Ida A. Giebelen & Tom van der Poll

  2. Department of Anesthesiology, University Medical Center Utrecht, P.O. Box 85500, 3508, Utrecht, GA, The Netherlands

    Lucienne C. Lemaire

  3. Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105, Amsterdam, AZ, The Netherlands

    Ida A. Giebelen & Tom van der Poll

  4. Research Department, Brahms AG, Neuendorfstrasse 25, 16761, Hennigsdorf/Berlin, Germany

    Joachim Struck, Nils G. Morgenthaler & Jana Papassotiriou

  5. CombinatoRx, Inc., 245 st., 16th floor, 02142, Cambridge, MA, USA

    Peter J. Elliott

  6. Sirtris Pharmaceuticals, 790 Memorial Drive, 02139, Cambridge, MA, USA

    Peter J. Elliott

Authors
  1. Martijn D. de Kruif
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  2. Lucienne C. Lemaire
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  3. Ida A. Giebelen
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  4. Joachim Struck
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  5. Nils G. Morgenthaler
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  6. Jana Papassotiriou
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  7. Peter J. Elliott
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  8. Tom van der Poll
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Corresponding author

Correspondence to Martijn D. de Kruif.

Additional information

This study was supported by research funding from CombinatoRx, Inc., Cambridge, MA, USA. One of the authors (Peter J. Elliott) was employed by CombinatoRx at the time of study design and completion. Currently, he is employed elsewhere but he is still a stockholder of CombinatoRx. Joachim Struck, Nils G. Morgenthaler and Jana Papassotiriou are employed by Brahms AG, Hennigsdorf, Germany.

This article is discussed in the editorial available at: http://dx.doi.org/10.1007/s00134-007-0956-9.

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de Kruif, M.D., Lemaire, L.C., Giebelen, I.A. et al. The influence of corticosteroids on the release of novel biomarkers in human endotoxemia. Intensive Care Med 34, 518–522 (2008). https://doi.org/10.1007/s00134-007-0955-x

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  • DOI: https://doi.org/10.1007/s00134-007-0955-x

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