Patients with chronic inflammatory disorders, including infections, inflammatory bowel disease, arthritis and cancer, commonly become anemic. The anemia can make them sicker, is sometimes severe enough to require a blood transfusion, and responds only partially to current treatments. Researchers at Children's Hospital Boston, Harvard Medical School, and the European Molecular Biology Laboratory have unraveled the complicated biology behind this type of anemia and propose new targets for drug development. They report their findings in the April 18 edition of Nature Genetics.

A Children's Hospital team led by Cindy Roy in CHB's Division of Hematology/Oncology previously showed that anemia of chronic disease results from over-activation of hepcidin, a hormone involved in controlling iron in the body. Hepcidin is triggered by inflammation and may also help fight infection, both by directly inactivating pathogens and by reducing the amount of iron circulating in the blood. This "iron withholding" deprives infectious pathogens of a nutrient they need to proliferate, but it also reduces the iron available to developing red blood cells. As a result, patients become anemic.

Now, Roy and colleagues have identified a key regulator of hepcidin, a protein called HFE. The researchers showed that genetically engineered mice with deficiencies in HFE maintained elevated levels of iron in the blood during inflammation. "What we've shown is that unless you have the HFE protein, you can't mount this iron-withholding response," says Roy, who holds a doctorate in cell biology. "By turning off HFE, you turn off hepcidin and it's ability to respond to inflammation."

Anemia of chronic disease is often treated with iron or erythropoietin, a growth hormone for red blood cells, but neither is fully effective because hepcidin blocks the necessary iron from getting to the red cells. "An important n
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Contact: Mary-Ellen Shay
mary.shay@childrens.harvard.edu
617-355-6420
Children's Hospital Boston
18-Apr-2004