title: The influence of corticosteroids on the release of novel biomarkers in human endotoxemia.
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.
  
  
  METHODS
  Prospective, open-label study in a specialized clinical research unit of a university hospital.
  
  
  METHODS
  Thirty-two healthy male volunteers.
  
  
  METHODS
  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.
  
  
  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.
authors: Center for Experimental and Molecular Medicine, Room G2-132, Academic Medical Center, Meibergdreef 9, 1105 Amsterdam, AZ, The Netherlands. m.d.dekruif@amc.uva.nl
authors: Martijn D
authors: MD
authors: de Kruif
authors: Lucienne C
authors: LC
authors: Lemaire
authors: Ida A
authors: IA
authors: Giebelen
authors: Joachim
authors: J
authors: Struck
authors: Nils G
authors: NG
authors: Morgenthaler
authors: Jana
authors: J
authors: Papassotiriou
authors: Peter J
authors: PJ
authors: Elliott
authors: Tom
authors: T
authors: van der Poll
mesh_terms: D000284:Administration, Oral; D053607:Adrenomedullin / Q000097:blood; D000328:Adult; D001127:Arginine Vasopressin / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D036361:Peptide Hormones / Q000097:blood*; D011239:Prednisolone / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D018805:Sepsis / Q000097:blood / Q000188:drug therapy; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D036361:Peptide Hormones; D011498:Protein Precursors; C088633:proadrenomedullin; D001127:Arginine Vasopressin; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor; D002116:Calcitonin; D011239:Prednisolone; D015740:Calcitonin Gene-Related Peptide