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Blood. 2014 Oct 23;124(17):2643-6. doi: 10.1182/blood-2014-03-559484. Epub 2014 Aug 27.

Effect of the antihepcidin Spiegelmer lexaptepid on inflammation-induced decrease in serum iron in humans.

Author information

1
Department of Intensive Care Medicine, and Radboud Institute for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands;
2
NOXXON Pharma AG, Berlin, Germany;
3
Radboud Institute for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Laboratory Medicine, Laboratory of Genetic, Endocrine and Metabolic Diseases, Radboud University Medical Center, Nijmegen, The Netherlands; Hepcidinanalysis.com, Nijmegen, The Netherlands; and.
4
Department of Intensive Care Medicine, and Radboud Institute for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Anesthesiology, Radboud University Medical Center, Nijmegen, The Netherlands.

Abstract

Increased hepcidin production is key to the development of anemia of inflammation. We investigated whether lexaptepid, an antihepcidin l-oligoribonucleotide, prevents the decrease in serum iron during experimental human endotoxemia. This randomized, double-blind, placebo-controlled trial was carried out in 24 healthy males. At T = 0 hours, 2 ng/kg Escherichia coli lipopolysaccharide was intravenously administered, followed by an intravenous injection of 1.2 mg/kg lexaptepid or placebo at T = 0.5 hours. The lipopolysaccharide-induced inflammatory response was similar in subjects treated with lexaptepid or placebo regarding clinical and biochemical parameters. At T = 9 hours, serum iron had increased by 15.9 ± 9.8 µmol/L from baseline in lexaptepid-treated subjects compared with a decrease of 8.3 ± 9.0 µmol/L in controls (P < .0001). This study delivers proof of concept that lexaptepid achieves clinically relevant hepcidin inhibition enabling investigations in the treatment of anemia of inflammation. This trial was registered at www.clinicaltrial.gov as #NCT01522794.

PMID:
25163699
PMCID:
PMC4208279
DOI:
10.1182/blood-2014-03-559484
[Indexed for MEDLINE]
Free PMC Article

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