Anemia of inflammation (AI, anemia of chronic disease) is a common complication of a wide variety of inflammatory conditions including infections and connective tissue diseases. Because the iron regulatory protein hepcidin is increased during inflammation and overexpression of hepcidin recapitulates many of the features of AI, hepcidin is currently believed to be the primary mediator of AI. Furthermore, Sasu and colleagues showed that blocking hepcidin could improve AI (Blood, Vol. 115, No. 17, pp. 3616-24). To test whether hepcidin is indeed necessary for the development of AI, we used two models of AI in hepcidin knockout mice. The first model, using heat-killed Brucella abortus to model brucellosis, is the same as that used by Sasu and colleagues. The second model uses complete Freund's adjuvant to model Mycobacterial disease. We showed that absence of hepcidin did not protect against the development of anemia. Furthermore, we show that this was an iron restricted anemia arguing that iron sequestration can occur independent of hepcidin. This study indicates that hepcidin may not be the central mediator in all AI. Future research will be needed to determine why the anti-hepcidin treatment used by Sasu and colleagues was able to improve the anemia.
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Asterisk with author names denotes non-ASH members.