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

Abstract

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 57 Fe-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. The study was registered as a prospective observational trial at clinicaltrials.gov identifier: 02175888 . The study was funded by the International Atomic Energy Agency.

The <i>TMPRSS6</i> variant (SNP rs855791) affects iron metabolism and oral iron absorption – a stable iron isotope study in Taiwanese women

“…35 Such a compensatory mechanism was suggested in a recent study in women in whom an acute inflammatory stimulus increased Hep but did not affect iron absorption. 36 Our findings suggest that, at low serum ferritin concentrations, women with the TT variant have lower iron absorption, whereas when iron stores are replete, they may be less able to downregulate iron absorption compared to the CC variant. Our variant-specific FIA correction to serum ferritin uses a similar approach as the original formula of Cook et al 30 used to correct dietary absorption measurements for the individual iron status; that formula employs a slope of -1 between log FIA and log SF.…”

Treatment of anemia in cancer patients undergoing chemotherapy with intravenous ferric carboxymaltose without erythropoiesis-stimulating agents

“…Pro-inflammatory cytokines are also released leading in turn to increased release of hepcidin; a small (25 amino acids) peptide produced by the liver. 28 Hepcidin is a regulator of iron homeostasis; 29 , 30 it binds to ferroportin-expressing cells inhibiting iron transport across cell membranes and decreasing accessibility to the iron stores. 31 At high enough circulating levels, it also impairs gastrointestinal absorption of dietary iron.…”

Reduced iron export associated with hepcidin resistance can explain the iron overload spectrum in ferroportin disease

“…2 Recent data from iron supplementation studies in humans would be in a line with different effects of hepcidin on macrophage iron retention versus enterocyte iron absorption, as those studies demonstrate that inflammation induced hepcidin expression resulted in macrophage iron retention but had only little effects on duodenal iron absorption. 35 The common cause of primary iron overload is uncontrolled intestinal iron absorption, where iron repletion fails to inhibit further duodenal iron uptake. In hemochromatosis this is thought to result from impaired iron sensing and hepcidin production.…”