Time-course analysis of serum hepcidin, iron and cytokines in a C282Y homozygous patient with Schnitzler's syndrome treated with IL-1 receptor antagonist.
It is currently unknown if the increase of the hepatic iron regulatory hormone hepcidin during inflammation in man depends on an intact HFE-protein. Here we describe the temporal relationship of serum hepcidin, serum iron and cytokines in a patient with HFE-related (C282Y homozygous) hereditary hemochromatosis who was treated for an auto-inflammatory condition, i.e. variant Schnitzler's syndrome, with the potent anti-inflammatory cytokine inter-leukin-1 receptor antagonist (IL-1ra, anakinra). The patient had bouts of fever with peaking serum IL-6 concentrations followed by peaking serum hepcidin levels, while serum iron was low. Upon treatment, these peaks disappeared and hepcidin levels became non-detectable, consistent with HFE deficiency. In conclusion, this in vivo human model: i) supports the importance of an HFE-independent IL-6-hepcidin axis in the development of hypoferremia and anemia of inflammation; and ii) suggests that chronic inflammation protects patients with HFE-related hereditary hemochromatosis from iron accumulation.
van Deuren
Marcel
M
Department of Clinical Chemistry, 441 Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands.
Kroot
Joyce J C
JJ
Swinkels
Dorine W
DW
D023181:Antimicrobial Cationic Peptides / Q000097:blood* / Q000235:genetics; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D006432:Hemochromatosis / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000097:blood* / Q000235:genetics; D006720:Homozygote; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000097:blood*; D007501:Iron / Q000097:blood*; D008297:Male; D008565:Membrane Proteins / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D020125:Mutation, Missense; D019873:Schnitzler Syndrome / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D013997:Time Factors
D023181:Antimicrobial Cationic Peptides; D018501:Antirheumatic Agents; C578702:HAMP protein, human; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; C508600:IL6 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D008565:Membrane Proteins; D007501:Iron