Time-course analysis of serum hepcidin, iron and cytokines in a C282Y homozygous patient with Schnitzler's syndrome treated with IL-1 receptor antagonist

Haematologica. 2009 Sep;94(9):1297-300. doi: 10.3324/haematol.2009.005975. Epub 2009 Jul 16.


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.

Publication types

  • Case Reports

MeSH terms

  • Antimicrobial Cationic Peptides / blood*
  • Antimicrobial Cationic Peptides / genetics
  • Antirheumatic Agents / administration & dosage*
  • Hemochromatosis Protein
  • Hemochromatosis* / blood
  • Hemochromatosis* / drug therapy
  • Hemochromatosis* / genetics
  • Hepcidins
  • Histocompatibility Antigens Class I / blood*
  • Histocompatibility Antigens Class I / genetics
  • Homozygote
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / administration & dosage*
  • Interleukin-6 / blood*
  • Iron / blood*
  • Male
  • Membrane Proteins / blood*
  • Membrane Proteins / genetics
  • Middle Aged
  • Mutation, Missense*
  • Schnitzler Syndrome* / blood
  • Schnitzler Syndrome* / drug therapy
  • Schnitzler Syndrome* / genetics
  • Time Factors


  • Antimicrobial Cationic Peptides
  • Antirheumatic Agents
  • HAMP protein, human
  • HFE protein, human
  • Hemochromatosis Protein
  • Hepcidins
  • Histocompatibility Antigens Class I
  • IL6 protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-6
  • Membrane Proteins
  • Iron