title: Effect of the antihepcidin Spiegelmer lexaptepid on inflammation-induced decrease in serum iron in humans.
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.
authors.affiliation: Department of Intensive Care Medicine, and Radboud Institute for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands;
authors.forename: Lucas T
authors.initials: LT
authors.lastname: van Eijk
authors.affiliation: Department of Intensive Care Medicine, and Radboud Institute for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands;
authors.forename: Aaron S E
authors.initials: AS
authors.lastname: John
authors.affiliation: NOXXON Pharma AG, Berlin, Germany;
authors.forename: Frank
authors.initials: F
authors.lastname: Schwoebel
authors.affiliation: NOXXON Pharma AG, Berlin, Germany;
authors.forename: Luciana
authors.initials: L
authors.lastname: Summo
authors.affiliation: NOXXON Pharma AG, Berlin, Germany;
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Vauléon
authors.affiliation: NOXXON Pharma AG, Berlin, Germany;
authors.forename: Stefan
authors.initials: S
authors.lastname: Zöllner
authors.affiliation: 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.
authors.forename: Coby M
authors.initials: CM
authors.lastname: Laarakkers
authors.affiliation: 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.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Kox
authors.affiliation: Department of Intensive Care Medicine, and Radboud Institute for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands;
authors.forename: Johannes G
authors.initials: JG
authors.lastname: van der Hoeven
authors.affiliation: 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.
authors.forename: Dorine W
authors.initials: DW
authors.lastname: Swinkels
authors.affiliation: NOXXON Pharma AG, Berlin, Germany;
authors.forename: Kai
authors.initials: K
authors.lastname: Riecke
authors.affiliation: Department of Intensive Care Medicine, and Radboud Institute for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands;
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
mesh_terms: D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D004311:Double-Blind Method; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D064451:Hepcidins / Q000037:antagonists & inhibitors / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000139:chemically induced / Q000517:prevention & control*; D007275:Injections, Intravenous; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood; D016753:Interleukin-10; D015850:Interleukin-6 / Q000097:blood; D007501:Iron / Q000097:blood*; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D008297:Male; D008657:Metabolic Clearance Rate; D009843:Oligoribonucleotides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D064451:Hepcidins; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009843:Oligoribonucleotides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002097:C-Reactive Protein; C581096:NOX-H94; D007501:Iron