The opposing effects of acute inflammation and iron deficiency anemia on serum hepcidin and iron absorption in young women

Hepatic hepcidin synthesis is stimulated by inflammation but inhibited during iron deficiency anemia (IDA). In humans, the relative strength of these opposing signals on serum hepcidin and the net effect on iron absorption and systemic iron recycling is uncertain. In this prospective, 45-day study, in young women (n=46; age 18-49 years) with or without IDA, we compared iron and inflammation markers, serum hepcidin and erythrocyte iron incorporation from Fe-57-labeled test meals, before and 8, 24 and 36 hours (h) after influenza/DPT vaccination as an acute inflammatory stimulus. Compared to baseline, at 24-36 h after vaccination: 1) interleukin-6 increased 2-3-fold in both groups (P<0.001); 2) serum hepcidin increased >2-fold in the non-anemic group (P<0.001), but did not significantly change in the IDA group; 3) serum iron decreased in the non-anemic group (P<0.05) but did not change in the IDA group; and 4) erythrocyte iron incorporation did not change in either of the two groups, but was approximately 2-fold higher in the IDA group both before and after vaccination (P<0.001). In this study, mild acute inflammation did not increase serum hepcidin in women with IDA, suggesting low iron status and erythropoietic drive offset the inflammatory stimulus on hepcidin expression. In non-anemic women, inflammation increased serum hepcidin and produced mild hypoferremia, but did not reduce dietary iron absorption, suggesting iron-recycling macrophages are more sensitive than the enterocyte to high serum hepcidin during inflammation.