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Effect of the anti-hepcidin 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

Key points

  • Lexaptepid modulates the inflammation-induced decrease in serum iron during experimental human endotoxemia.

  • Hepcidin targeting with the novel compound lexaptepid may be a viable approach to the treatment of anemia of inflammation in humans,

Abstract

Increased hepcidin production is key to the development of anemia of inflammation. We investigated whether lexaptepid, an anti-hepcidin 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 flu-like symptoms, body temperature, C-reactive protein, leucocyte counts and cytokine concentrations. 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<0.0001). 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 #NCT01522794.

  • Submitted March 28, 2014.
  • Accepted July 23, 2014.