IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin
Elizabeta Nemeth, … , Bente K. Pedersen, Tomas Ganz
Elizabeta Nemeth, … , Bente K. Pedersen, Tomas Ganz
Published May 1, 2004
Citation Information: J Clin Invest. 2004;113(9):1271-1276. https://doi.org/10.1172/JCI20945.
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Article Hematology

IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin

Abstract

Hypoferremia is a common response to systemic infections or generalized inflammatory disorders. In mouse models, the development of hypoferremia during inflammation requires hepcidin, an iron regulatory peptide hormone produced in the liver, but the inflammatory signals that regulate hepcidin are largely unknown. Our studies in human liver cell cultures, mice, and human volunteers indicate that IL-6 is the necessary and sufficient cytokine for the induction of hepcidin during inflammation and that the IL-6–hepcidin axis is responsible for the hypoferremia of inflammation.

Authors

Elizabeta Nemeth, Seth Rivera, Victoria Gabayan, Charlotte Keller, Sarah Taudorf, Bente K. Pedersen, Tomas Ganz

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IL-6 infusion increases urinary hepcidin and decreases serum iron in hum...
IL-6 infusion increases urinary hepcidin and decreases serum iron in humans. Six subjects were infused with rhIL-6 for 3 hours at the rate of 30 ∝g/h. Urine and serum samples were collected: prior to infusion at 0 hours, at the end of the infusion (3 h inf), 2 hours after the infusion (2 h after), and 24 hours after the infusion (24 h). (A) Serum IL-6 concentrations. (B) Urinary hepcidin levels. Thick line represents the geometric mean. The increase in hepcidin at 2 hours after infusion is highly significant (P < 0.001 by one-way RM ANOVA). (C) Serum iron concentration. (D) Serum transferrin saturation. Thick lines represent the arithmetic mean. The decreases in serum iron concentration and transferrin saturation at 2 hours after infusion are both highly significant compared with preinfusion values (both P < 0.001 by one-way RM ANOVA). creat, creatinine.