IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin.
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.
Nemeth
Elizabeta
E
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California, USA.
Rivera
Seth
S
Gabayan
Victoria
V
Keller
Charlotte
C
Taudorf
Sarah
S
Pedersen
Bente K
BK
Ganz
Tomas
T
D000740:Anemia / Q000209:etiology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis* / Q000652:urine; D002460:Cell Line; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology; D064451:Hepcidins; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D019189:Iron Metabolism Disorders / Q000473:pathology; D007728:Kupffer Cells / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D064451:Hepcidins; D015850:Interleukin-6; D012333:RNA, Messenger; D007501:Iron