1. Effect of the antihepcidin Spiegelmer lexaptepid on inflammation-induced decrease in serum iron in humans
- Author
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Frank Schwoebel, Matthijs Kox, Stefan Zöllner, Coby M. Laarakkers, Kai Riecke, Aaron John, Luciana Summo, Dorine W. Swinkels, Stephanie Vauléon, Lucas T. van Eijk, Peter Pickkers, and Johannes G. van der Hoeven
- Subjects
Lipopolysaccharides ,Male ,Lipopolysaccharide ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Anti-Inflammatory Agents ,Biochemistry ,chemistry.chemical_compound ,Leukocyte Count ,biology ,medicine.diagnostic_test ,Hematology ,Interleukin-10 ,C-Reactive Protein ,Treatment Outcome ,Injections, Intravenous ,Serum iron ,Tumor necrosis factor alpha ,medicine.symptom ,Adult ,medicine.medical_specialty ,Adolescent ,Anemia ,Metabolic Clearance Rate ,Iron ,Immunology ,Inflammation ,Placebo ,Young Adult ,Double-Blind Method ,Hepcidins ,Hepcidin ,Internal medicine ,medicine ,Humans ,Oligoribonucleotides ,business.industry ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,C-reactive protein ,Cell Biology ,medicine.disease ,Endotoxemia ,Interleukin 1 Receptor Antagonist Protein ,Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,Endocrinology ,chemistry ,biology.protein ,business - Abstract
Contains fulltext : 136275.pdf (Publisher’s version ) (Closed access) 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 micromol/L from baseline in lexaptepid-treated subjects compared with a decrease of 8.3 +/- 9.0 micromol/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.
- Published
- 2014
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