Key ACTEMRA/RoACTEMRA publication summaries
IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin
Nemeth E, Rivera S, Gabayan V, Charlotte K, Taudorf S, Pedersen BK, Ganz T.
J Clin Invest 2004; 113:1271–1276.
Patients with systemic infections or generalised inflammatory disorders commonly have low serum levels of iron (hypoferremia). Prior to this study, evidence from mouse models had indicated that hepcidin – an iron regulatory peptide hormone produced in the liver – plays a central role in the development of inflammation-associated hypoferremia. However, the specific signalling involved in the regulation of hepcidin was unclear.
In this article, the authors describe the elucidation of IL-6 as the primary mediator of hepcidin induction during inflammation. A series of in vitro and in vivo studies showed that IL-6, but not IL-1 or TNF-α, rapidly increases hepcidin excretion and induces hypoferremia in humans.
Hypoferremia is associated with a reduction in haemoglobin synthesis due to a decrease in iron supply and can eventually result in anaemia. The role of IL-6 in the hepcidin regulation pathway is therefore further supported by observations of anaemia in mice bred for overexpression of IL-6, and in rats and cancer patients repeatedly administered IL-6.
The authors conclude by noting that interventions targeting the IL-6–hepcidin pathway could be useful for therapy of anaemia associated with hypoferremia of inflammation.