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,
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.
- Copyright © 2014 American Society of Hematology