Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS.
Hepatic peptide hormone hepcidin is the key regulator of iron metabolism and the mediator of anemia of inflammation. Previous studies indicated that interleukin-6 (IL-6) mediates hepcidin increase and consequent hypoferremia during inflammation. Here we used an in vivo human endotoxemia model to analyze the effects of lipopolysaccharide (LPS) as a more upstream inflammation activator. The temporal associations between plasma cytokines, hepcidin levels, and serum iron parameters were studied in 10 healthy individuals after LPS injection. IL-6 was dramatically induced within 3 hours after injection, and urinary hepcidin peaked within 6 hours, followed by a significant decrease in serum iron. Serum prohepcidin showed no significant change within a 22-hour time frame. These in vivo human results confirm the importance of the IL-6-hepcidin axis in the development of hypoferremia in inflammation and highlight the rapid responsiveness of this iron regulatory system.
Kemna
Erwin
E
Department of Clinical Chemistry 564, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. e.kemna@akc.umcn.nl
Pickkers
Peter
P
Nemeth
Elizabeta
E
van der Hoeven
Hans
H
Swinkels
Dorine
D
D000293:Adolescent; D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000652:urine*; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000097:blood*; D019446:Endotoxemia / Q000097:blood* / Q000139:chemically induced; D005260:Female; D064451:Hepcidins; D006801:Humans; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000097:blood; D007501:Iron / Q000097:blood*; D008070:Lipopolysaccharides; D008297:Male; D012016:Reference Values; D013997:Time Factors
D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; C578702:HAMP protein, human; D064451:Hepcidins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D002097:C-Reactive Protein; D007501:Iron