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

Intensive Care Med. 2008 Mar;34(3):518-22. doi: 10.1007/s00134-007-0955-x. Epub 2007 Dec 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adrenomedullin / blood
  • Adult
  • Arginine Vasopressin / blood
  • Atrial Natriuretic Factor / blood
  • Biomarkers / blood
  • Calcitonin / blood
  • Calcitonin Gene-Related Peptide
  • Dose-Response Relationship, Drug
  • Endotoxemia / blood*
  • Endotoxemia / chemically induced
  • Endotoxemia / drug therapy*
  • Humans
  • Inflammation Mediators / blood
  • Injections, Intravenous
  • Lipopolysaccharides / pharmacology
  • Male
  • Peptide Hormones / blood*
  • Prednisolone / blood
  • Prednisolone / pharmacokinetics
  • Prednisolone / pharmacology*
  • Prospective Studies
  • Protein Precursors / blood*
  • Sepsis / blood
  • Sepsis / drug therapy
  • Severity of Illness Index

Substances

  • Biomarkers
  • CALCA protein, human
  • Inflammation Mediators
  • Lipopolysaccharides
  • Peptide Hormones
  • Protein Precursors
  • proadrenomedullin
  • Arginine Vasopressin
  • Adrenomedullin
  • Atrial Natriuretic Factor
  • Calcitonin
  • Prednisolone
  • Calcitonin Gene-Related Peptide