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, 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
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.
© 2014 by The American Society of Hematology.
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Source: PubMed