Targeting the hepcidin-ferroportin axis to develop new treatment strategies for anemia of chronic disease and anemia of inflammation

Am J Hematol. 2012 Apr;87(4):392-400. doi: 10.1002/ajh.23110. Epub 2012 Jan 31.

Abstract

Anemia of chronic disease (ACD) or anemia of inflammation is prevalent in patients with chronic infection, autoimmune disease, cancer, and chronic kidney disease. ACD is associated with poor prognosis and lower quality of life. Management of ACD using intravenous iron and erythropoiesis stimulating agents are ineffective for some patients and are not without adverse effects, driving the need for new alternative therapies. Recent advances in our understanding of the molecular mechanisms of iron regulation reveal that increased hepcidin, the iron regulatory hormone, is a key factor in the development of ACD. In this review, we will summarize the role of hepcidin in iron homeostasis, its contribution to the pathophysiology of ACD, and novel strategies that modulate hepcidin and its target ferroportin for the treatment of ACD.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Anemia / drug therapy*
  • Anemia / etiology
  • Anemia / physiopathology
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use
  • Antimicrobial Cationic Peptides / antagonists & inhibitors*
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / immunology
  • Antimicrobial Cationic Peptides / physiology
  • Antimicrobial Cationic Peptides / toxicity
  • Bone Morphogenetic Protein 6 / antagonists & inhibitors
  • Bone Morphogenetic Protein 6 / physiology
  • Cation Transport Proteins / agonists*
  • Cation Transport Proteins / physiology
  • Chronic Disease
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • GPI-Linked Proteins / antagonists & inhibitors
  • GPI-Linked Proteins / physiology
  • Hemochromatosis Protein
  • Hepcidins
  • Homeostasis
  • Humans
  • Inflammation / blood*
  • Inflammation / physiopathology
  • Interleukin-6 / antagonists & inhibitors
  • Iron / metabolism*
  • Mice
  • Molecular Targeted Therapy*
  • Pyrazoles / therapeutic use
  • Pyrimidines / therapeutic use
  • RNA, Small Interfering / therapeutic use
  • STAT3 Transcription Factor / antagonists & inhibitors
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Smad Proteins / antagonists & inhibitors
  • Smad Proteins / physiology
  • Therapies, Investigational*
  • Vitamin D / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Antimicrobial Cationic Peptides
  • BMP6 protein, human
  • Bone Morphogenetic Protein 6
  • Cation Transport Proteins
  • GPI-Linked Proteins
  • HAMP protein, human
  • HJV protein, human
  • Hamp protein, mouse
  • Hemochromatosis Protein
  • Hepcidins
  • IL6 protein, human
  • Interleukin-6
  • LDN 193189
  • Pyrazoles
  • Pyrimidines
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Smad Proteins
  • metal transporting protein 1
  • Vitamin D
  • Iron