title: Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS.
abstract: 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.
authors.affiliation: Department of Clinical Chemistry 564, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. e.kemna@akc.umcn.nl
authors.forename: Erwin
authors.initials: E
authors.lastname: Kemna
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
authors.forename: Elizabeta
authors.initials: E
authors.lastname: Nemeth
authors.forename: Hans
authors.initials: H
authors.lastname: van der Hoeven
authors.forename: Dorine
authors.initials: D
authors.lastname: Swinkels
mesh_terms: 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
chemical_list: D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; C578702:HAMP protein, human; D064451:Hepcidins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D002097:C-Reactive Protein; D007501:Iron