The influence of corticosteroids on the release of novel biomarkers in human endotoxemia.
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.
de Kruif
Martijn D
MD
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
Lemaire
Lucienne C
LC
Giebelen
Ida A
IA
Struck
Joachim
J
Morgenthaler
Nils G
NG
Papassotiriou
Jana
J
Elliott
Peter J
PJ
van der Poll
Tom
T
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
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