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

Lucas T van Eijk, Aaron S E John, Frank Schwoebel, Luciana Summo, Stéphanie Vauléon, Stefan Zöllner, Coby M Laarakkers, Matthijs Kox, Johannes G van der Hoeven, Dorine W Swinkels, Kai Riecke, Peter Pickkers

Journal: Blood 2015;124(17):2643-6

PMID: 25163699

Free Full Text on Elsevier Science View on PubMed

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.

Address: Department of Intensive Care Medicine, and Radboud Institute for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands;; NOXXON Pharma AG, Berlin, Germany;; 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.; 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.

DOI: 10.1182/blood-2014-03-559484

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MeSH Terms: Adolescent, Adult, Anti-Inflammatory Agents, C-Reactive Protein, Double-Blind Method, Endotoxemia, Hepcidins, Humans, Inflammation, Injections, Intravenous, Interleukin 1 Receptor Antagonist Protein, Interleukin-10, Interleukin-6, Iron, Leukocyte Count, Lipopolysaccharides, Male, Metabolic Clearance Rate, Oligoribonucleotides, Treatment Outcome, Tumor Necrosis Factor-alpha, Young Adult