Hepcidin independent anemia of inflammation

Because hepcidin overproduction mimics anemia of inflammation and absence of hepcidin protects against the acute hypoferremia seen in response to inflammation, hepcidin is presumed to be necessary for the development of anemia of inflammation (AI, anemia of chronic disease). However no independent studies have tested this hypothesis. Using two mouse models of anemia of inflammation and hepcidin deficient mice, we sought to determine whether hepcidin is necessary for the development of anemia of inflammation. Hepcidin knockout mice maintained on a standard iron diet were largely protected against AI. However, these mice have severe iron overload prior to the onset of inflammation, which may protect them against AI. We therefore sought to prevent the development of iron overload prior to the onset of inflammation by restricting dietary iron immediately after weaning. Hepcidin knockout mice without baseline iron overload developed anemia as severe as wild type mice and this anemia was iron restricted. Therefore, hepcidin is not necessary for the development of anemia in some inflammatory diseases. Hepcidin antagonists may not be effective in treating some patients with AI.