Skip to main content

Molecular and clinical aspects of iron homeostasis: from anemia to hemochromatosis

Molekulare und klinische Aspekte des Eisenstoffwechsels. Von der Anämie bis zur Hämochromatose

Wiener klinische Wochenschrift volume 118, pages 442–462 (2006)Cite this article

Zusammenfassung

Die Entdeckung zahlreicher neuer Gene, deren Produkte am Eisenstoffwechsel und an dessen komplexer Regulation beteiligt sind, hat unser Wissen in diesem Bereich in den letzten Jahren rasch zunehmen lassen. Störungen der Eisenhomöostase gehören zu den häufigsten pathologischen Veränderungen im klinischen Alltag und können sich auf den Gesundheitszustand und auf die Lebenserwartung eines Patienten negativ auswirken. Daher ist ein fundiertes Wissen über den Eisenstoffwechsel sowie über die pathophysiologischen und klinischen Aspekte von Eisenüberladung, -mangel und -fehlverteilung von großer medizinischer Bedeutung. Diese Arbeit fasst den gegenwärtigen Wissensstand im Bereich des Eisenstoffwechsels zusammen, wobei der Schwerpunkt auf klinisch relevanten Fakten von hereditärer Hämochromatose, sekundärer Eisenüberladung, Eisenmangelanämie, Anämie der chronischen Erkrankung und Anämie der kritischen Erkrankung liegt. Darüber hinaus werden die Berührungspunkte von Eisenstoffwechsel und Immunsystem dargestellt, soweit sie den Zusammenhang zwischen Eisenstatus und Risiko für Infektionen und Malignome betreffen.

Summary

The discovery in recent years of a plethora of new genes whose products are implicated in iron homeostasis has led to rapid expansion of our knowledge in the field of iron metabolism and its underlying complex regulation in both health and disease. Abnormalities of iron metabolism are among the most common disorders encountered in practical medicine and may have significant negative impact on physical condition and life expectancy. Basic insights into the principles of iron homeostasis and the pathophysiological and clinical consequences of iron overload, iron deficiency and misdistribution are thus of crucial importance in modern medicine. This review summarizes our current understanding of human iron metabolism and focuses on the clinically relevant features of hereditary and secondary hemochromatosis, iron deficiency anemia, anemia of chronic disease and anemia of critical illness. The interconnections between iron metabolism and immunity are also addressed, in as much as they may affect the risk and course of infections and malignancies.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  • Weiss G (2002) Iron and immunity: a double-edged sword. Eur J Clin Invest 32 [Suppl 1]: 70

    PubMed  CAS  Article  Google Scholar 

  • Hentze MW, Muckenthaler MU, Andrews NC (2004) Balancing acts: molecular control of mammalian iron metabolism. Cell 117: 285

    PubMed  CAS  Article  Google Scholar 

  • Pantopoulos K (2005) Regulation of Iron Metabolism. In: Weiss GVRG, Hershko C (eds) Anemia of chronic disease, Vol 30. CRC Press, Taylor & Francis Group, Boca Raton, p 1

    Google Scholar 

  • Weiss G, Goodnough LT (2005) Anemia of chronic disease. N Engl J Med 352: 1011

    PubMed  CAS  Article  Google Scholar 

  • Pietrangelo A (2004) Hereditary hemochromatosis – a new look at an old disease. N Engl J Med 350: 2383

    PubMed  CAS  Article  Google Scholar 

  • Yano M, Hayashi H, Yoshioka K, Kohgo Y, Saito H, Niitsu Y, et al (2004) A significant reduction in serum alanine aminotransferase levels after 3-month iron reduction therapy for chronic hepatitis C: a multicenter, prospective, randomized, controlled trial in Japan. J Gastroenterol 39: 570

    PubMed  CAS  Article  Google Scholar 

  • Metwally MA, Zein CO, Zein NN (2004) Clinical significance of hepatic iron deposition and serum iron values in patients with chronic hepatitis C infection. Am J Gastroenterol 99: 286

    PubMed  CAS  Article  Google Scholar 

  • Theurl I, Zoller H, Obrist P, Datz C, Bachmann F, Elliott RM, et al (2004) Iron regulates hepatitis C virus translation via stimulation of expression of translation initiation factor 3. J Infect Dis 190: 819

    PubMed  CAS  Article  Google Scholar 

  • Gordeuk VR, Delanghe JR, Langlois MR, Boelaert JR (2001) Iron status and the outcome of HIV infection: an overview. J Clin Virol 20: 111

    PubMed  CAS  Article  Google Scholar 

  • Kiechl S, Willeit J, Egger G, Poewe W, Oberhollenzer F (1997) Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study. Circulation 96: 3300

    PubMed  CAS  Google Scholar 

  • Tuomainen TP, Punnonen K, Nyyssonen K, Salonen JT (1998) Association between body iron stores and the risk of acute myocardial infarction in men. Circulation 97: 1461

    PubMed  CAS  Google Scholar 

  • Gaenzer H, Marschang P, Sturm W, Neumayr G, Vogel W, Patsch J, et al (2002) Association between increased iron stores and impaired endothelial function in patients with hereditary hemochromatosis. J Am Coll Cardiol 40: 2189

    PubMed  CAS  Article  Google Scholar 

  • Turoczi T, Jun L, Cordis G, Morris JE, Maulik N, Stevens RG, et al (2003) HFE mutation and dietary iron content interact to increase ischemia/reperfusion injury of the heart in mice. Circ Res 92: 1240

    PubMed  CAS  Article  Google Scholar 

  • Weinberg ED (1998) Patho-ecological implications of microbial acquisition of host iron. Reviews in Medical Microbiology 9: 171

    Google Scholar 

  • Weinberg ED (1999) Iron therapy and cancer. Kidney Int [Suppl] 69: S131

    CAS  Article  Google Scholar 

  • Weiss G (2002) Iron, infection and anemia – a classical triad. Wien Klin Wochenschr 114: 357

    PubMed  CAS  Google Scholar 

  • Feder JN, Penny DM, Irrinki A, Lee VK, Lebron JA, Watson N, et al (1998) The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding. Proc Natl Acad Sci USA 95: 1472

    PubMed  CAS  Article  Google Scholar 

  • Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, et al (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388: 482

    PubMed  CAS  Article  Google Scholar 

  • McKie AT, Barrow D, Latunde-Dada GO, Rolfs A, Sager G, Mudaly E, et al (2001) An iron-regulated ferric reductase associated with the absorption of dietary iron. Science 291: 1755

    PubMed  CAS  Article  Google Scholar 

  • Shayeghi M, Latunde-Dada GO, Oakhill JS, Laftah AH, Takeuchi K, Halliday N, et al (2005) Identification of an intestinal heme transporter. Cell 122: 789

    PubMed  CAS  Article  Google Scholar 

  • Poss KD, Tonegawa S (1997) Heme oxygenase 1 is required for mammalian iron reutilization. Proc Natl Acad Sci USA 94: 10919

    PubMed  CAS  Article  Google Scholar 

  • Theurl I, Fritsche G, Ludwiczek S, Garimorth K, Bellmann-Weiler R, Weiss G (2005) The macrophage: a cellular factory at the interphase between iron and immunity for the control of infections. Biometals 18: 359

    PubMed  CAS  Article  Google Scholar 

  • Weiss G (2002) Iron acquisition by the reticuloendothelial system. In: Templeton D (ed) Molecular and cellular iron transport. Marcel Dekker, New York, p 467

    Google Scholar 

  • Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, et al (2001) Identification of the haemoglobin scavenger receptor. Nature 409: 198

    PubMed  CAS  Article  Google Scholar 

  • Hvidberg V, Maniecki MB, Jacobsen C, Hojrup P, Moller HJ, Moestrup SK (2005) Identification of the receptor scavenging hemopexin-heme complexes. Blood 106: 2572

    PubMed  CAS  Article  Google Scholar 

  • Muckenthaler M, Gray NK, Hentze MW (1998) IRP-1 binding to ferritin mRNA prevents the recruitment of the small ribosomal subunit by the cap-binding complex eIF4F. Mol Cell 2: 383

    PubMed  CAS  Article  Google Scholar 

  • Guo B, Phillips JD, Yu Y, Leibold EA (1995) Iron regulates the intracellular degradation of iron regulatory protein 2 by the proteasome. J Biol Chem 270: 21645

    PubMed  CAS  Article  Google Scholar 

  • Donovan A, Lima CA, Pinkus JL, Pinkus GS, Zon LI, Robine S, et al (2005) The iron exporter ferroportin/Slc40 a1 is essential for iron homeostasis. Cell Metab 1: 191

    PubMed  CAS  Article  Google Scholar 

  • Wessling-Resnick M (2006) Iron imports. III. Transfer of iron from the mucosa into circulation. Am J Physiol Gastrointest Liver Physiol 290: G1

    PubMed  CAS  Article  Google Scholar 

  • Conrad ME, Umbreit JN (2002) Pathways of iron absorption. Blood Cells Mol Dis 29: 336

    PubMed  CAS  Article  Google Scholar 

  • Zoller H, Koch RO, Theurl I, Obrist P, Pietrangelo A, Montosi G, et al (2001) Expression of the duodenal iron transporters divalent-metal transporter 1 and ferroportin 1 in iron deficiency and iron overload. Gastroenterology 120: 1412

    PubMed  CAS  Article  Google Scholar 

  • Creagh AL, Tiong JW, Tian MM, Haynes CA, Jefferies WA (2005) Calorimetric studies of melanotransferrin (p97) and its interaction with iron. J Biol Chem 280: 15735

    PubMed  CAS  Article  Google Scholar 

  • Sekyere EO, Dunn LL, Rahmanto YS, Richardson DR (2006) Role of melanotransferrin in iron metabolism: studies using targeted gene disruption in vivo. Blood 107: 2599

    PubMed  CAS  Article  Google Scholar 

  • Trinder D, Oates PS, Thomas C, Sadleir J, Morgan EH (2000) Localisation of divalent metal transporter 1 (DMT1) to the microvillus membrane of rat duodenal enterocytes in iron deficiency, but to hepatocytes in iron overload. Gut 46: 270

    PubMed  CAS  Article  Google Scholar 

  • Anderson GJ, Frazer DM (2005) Hepatic iron metabolism. Semin Liver Dis 25: 420

    PubMed  CAS  Article  Google Scholar 

  • Gunshin H, Fujiwara Y, Custodio AO, Direnzo C, Robine S, Andrews NC (2005) Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver. J Clin Invest 115: 1258

    PubMed  CAS  Article  Google Scholar 

  • Andrews NC (1999) Disorders of iron metabolism. N Engl J Med 341: 1986

    PubMed  CAS  Article  Google Scholar 

  • Hagler L, Askew EW, Neville JR, Mellick PW, Coppes RI Jr, Lowder JF Jr (1981) Influence of dietary iron deficiency on hemoglobin, myoglobin, their respective reductases, and skeletal muscle mitochondrial respiration. Am J Clin Nutr 34: 2169

    PubMed  CAS  Google Scholar 

  • Weiss G (2005) Modification of iron regulation by the inflammatory response. Best Pract Res Clin Haematol 18: 183

    PubMed  CAS  Article  Google Scholar 

  • Theurl I, Ludwiczek S, Eller P, Seifert M, Artner E, Brunner P, et al (2005) Pathways for the regulation of body iron homeostasis in response to experimental iron overload. J Hepatol 43: 711

    PubMed  CAS  Article  Google Scholar 

  • Ludwiczek S, Theurl I, Bahram S, Schumann K, Weiss G (2005) Regulatory networks for the control of body iron homeostasis and their dysregulation in HFE mediated hemochromatosis. J Cell Physiol 204: 489

    PubMed  CAS  Article  Google Scholar 

  • Abouhamed M, Gburek J, Liu W, Torchalski B, Wilhelm A, Wolff NA, et al (2006) Divalent metal transporter 1 in the kidney proximal tubule is expressed in late endosomes/lysosomal membranes: implications for renal handling of protein-metal complexes. Am J Physiol Renal Physiol 290: F1525

    PubMed  CAS  Article  Google Scholar 

  • Canonne-Hergaux F, Gros P (2002) Expression of the iron transporter DMT1 in kidney from normal and anemic mk mice. Kidney Int 62: 147

    PubMed  CAS  Article  Google Scholar 

  • Wareing M, Ferguson CJ, Green R, Riccardi D, Smith CP (2000) In vivo characterization of renal iron transport in the anaesthetized rat. J Physiol 524 Pt 2: 581

    PubMed  CAS  Article  Google Scholar 

  • Yang J, Goetz D, Li JY, Wang W, Mori K, Setlik D, et al (2002) An iron delivery pathway mediated by a lipocalin. Mol Cell 10: 1045

    PubMed  CAS  Article  Google Scholar 

  • Mishra J, Mori K, Ma Q, Kelly C, Yang J, Mitsnefes M, et al (2004) Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 15: 3073

    PubMed  Article  Google Scholar 

  • Mishra J, Mori K, Ma Q, Kelly C, Barasch J, Devarajan P (2004) Neutrophil gelatinase-associated lipocalin: a novel early urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol 24: 307

    PubMed  CAS  Article  Google Scholar 

  • Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, et al (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365: 1231

    PubMed  CAS  Article  Google Scholar 

  • Wareing M, Ferguson CJ, Delannoy M, Cox AG, McMahon RF, Green R, et al (2003) Altered dietary iron intake is a strong modulator of renal DMT1 expression. Am J Physiol Renal Physiol 285: F1050

    PubMed  CAS  Google Scholar 

  • Ganz T, Nemeth E (2006) Iron imports. IV. Hepcidin and regulation of body iron metabolism. Am J Physiol Gastrointest Liver Physiol 290: G199

    PubMed  CAS  Article  Google Scholar 

  • Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I, et al (2002) The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 110: 1037

    PubMed  CAS  Article  Google Scholar 

  • Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, et al (2004) IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 113: 1271

    PubMed  CAS  Article  Google Scholar 

  • Nicolas G, Bennoun M, Porteu A, Mativet S, Beaumont C, Grandchamp B, et al (2002) Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci USA 99: 4596

    PubMed  CAS  Article  Google Scholar 

  • Viatte L, Nicolas G, Lou DQ, Bennoun M, Lesbordes-Brion JC, Canonne-Hergaux F, et al (2005) Chronic hepcidin induction causes hyposideremia and alters the pattern of cellular iron accumulation in hemochromatotic mice. Blood 107: 2952

    PubMed  Article  CAS  Google Scholar 

  • Knutson MD, Oukka M, Koss LM, Aydemir F, Wessling-Resnick M (2005) Iron release from macrophages after erythrophagocytosis is up-regulated by ferroportin 1 overexpression and down-regulated by hepcidin. Proc Natl Acad Sci USA 102: 1324

    PubMed  CAS  Article  Google Scholar 

  • Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, et al (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306: 2090

    PubMed  CAS  Article  Google Scholar 

  • Detivaud L, Nemeth E, Boudjema K, Turlin B, Troadec MB, Leroyer P, et al (2005) Hepcidin levels in humans are correlated with hepatic iron stores, hemoglobin levels, and hepatic function. Blood 106: 746

    PubMed  CAS  Article  Google Scholar 

  • Peyssonnaux C, Zinkernagel AS, Datta V, Lauth X, Johnson RS, Nizet V (2006) TLR-4 dependent hepcidin expression by myeloid cells in response to bacterial pathogens. Blood 107: 3727

    PubMed  CAS  Article  Google Scholar 

  • Babitt JL, Huang FW, Wrighting DM, Xia Y, Sidis Y, Samad TA, et al (2006) Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet 38: 531

    PubMed  CAS  Article  Google Scholar 

  • Huang FW, Pinkus JL, Pinkus GS, Fleming MD, Andrews NC (2005) A mouse model of juvenile hemochromatosis. J Clin Invest 115: 2187

    PubMed  CAS  Article  Google Scholar 

  • Niederkofler V, Salie R, Arber S (2005) Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload. J Clin Invest 115: 2180

    PubMed  CAS  Article  Google Scholar 

  • Zoller H, Cox TM (2005) Hemochromatosis: genetic testing and clinical practice. Clin Gastroenterol Hepatol 3: 945

    PubMed  CAS  Article  Google Scholar 

  • Beutler E, Hoffbrand AV, Cook JD (2003) Iron deficiency and overload. Hematology (Am Soc Hematol Educ Program): 40

  • Pietrangelo A (2004) The ferroportin disease. Blood Cells Mol Dis 32: 131

    PubMed  CAS  Article  Google Scholar 

  • Pietrangelo A, Caleffi A, Henrion J, Ferrara F, Corradini E, Kulaksiz H, et al (2005) Juvenile hemochromatosis associated with pathogenic mutations of adult hemochromatosis genes. Gastroenterology 128: 470

    PubMed  CAS  Article  Google Scholar 

  • Roetto A, Papanikolaou G, Politou M, Alberti F, Girelli D, Christakis J, et al (2003) Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet 33: 21

    PubMed  CAS  Article  Google Scholar 

  • Papanikolaou G, Samuels ME, Ludwig EH, MacDonald ML, Franchini PL, Dube MP, et al (2004) Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat Genet 36: 77

    PubMed  CAS  Article  Google Scholar 

  • Papanikolaou G, Tzilianos M, Christakis JI, Bogdanos D, Tsimirika K, MacFarlane J, et al (2005) Hepcidin in iron overload disorders. Blood 105: 4103

    PubMed  CAS  Article  Google Scholar 

  • Nemeth E, Roetto A, Garozzo G, Ganz T, Camaschella C (2005) Hepcidin is decreased in TFR2 hemochromatosis. Blood 105: 1803

    PubMed  CAS  Article  Google Scholar 

  • Corsi B, Cozzi A, Arosio P, Drysdale J, Santambrogio P, Campanella A, et al (2002) Human mitochondrial ferritin expressed in HeLa cells incorporates iron and affects cellular iron metabolism. J Biol Chem 277: 22430

    PubMed  CAS  Article  Google Scholar 

  • Zoller H, Theurl I, Koch RO, McKie AT, Vogel W, Weiss G (2003) Duodenal cytochrome b and hephaestin expression in patients with iron deficiency and hemochromatosis. Gastroenterology 125: 746

    PubMed  CAS  Article  Google Scholar 

  • Zoller H, Pietrangelo A, Vogel W, Weiss G (1999) Duodenal metal-transporter (DMT-1, NRAMP-2) expression in patients with hereditary haemochromatosis. Lancet 353: 2120

    PubMed  CAS  Article  Google Scholar 

  • Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC (2002) Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood 100: 3776

    PubMed  CAS  Article  Google Scholar 

  • Pietrangelo A (2005) Non-HFE hemochromatosis. Semin Liver Dis 25: 450

    PubMed  CAS  Article  Google Scholar 

  • Trinder D, Baker E (2003) Transferrin receptor 2: a new molecule in iron metabolism. Int J Biochem Cell Biol 35: 292

    PubMed  CAS  Article  Google Scholar 

  • Wallace DF, Summerville L, Lusby PE, Subramaniam VN (2005) First phenotypic description of transferrin receptor 2 knockout mouse, and the role of hepcidin. Gut 54: 980

    PubMed  CAS  Article  Google Scholar 

  • Cemonesi L, Forni GL, Soriani N, Lamagna M, Fermo I, Daraio F, et al (2005) Genetic and clinical heterogeneity of ferroportin disease. Br J Haematol 131: 663

    PubMed  Article  Google Scholar 

  • Bosio S, De Gobbi M, Roetto A, Zecchina G, Leonardo E, Rizzetto M, et al (2002) Anemia and iron overload due to compound heterozygosity for novel ceruloplasmin mutations. Blood 100: 2246

    PubMed  CAS  Article  Google Scholar 

  • Cox TM, Halsall DJ (2002) Hemochromatosis – neonatal and young subjects. Blood Cells Mol Dis 29: 411

    PubMed  CAS  Article  Google Scholar 

  • O'Neil J, Powell L (2005) Clinical aspects of hemochromatosis. Semin Liver Dis 25: 381

    PubMed  Article  Google Scholar 

  • Tavill AS (2001) Diagnosis and management of hemochromatosis. Hepatology 33: 1321

    PubMed  CAS  Article  Google Scholar 

  • Brandhagen DJ, Fairbanks VF, Baldus W (2002) Recognition and management of hereditary hemochromatosis. Am Fam Physician 65: 853

    PubMed  Google Scholar 

  • Altes A, Remacha AF, Sureda A, Martino R, Briones J, Brunet S, et al (2003) Patients with biochemical iron overload: causes and characteristics of a cohort of 150 cases. Ann Hematol 82: 127

    PubMed  CAS  Article  Google Scholar 

  • St Pierre TG, Clark PR, Chua-anusorn W, Fleming AJ, Jeffrey GP, Olynyk JK, et al (2005) Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood 105: 855

    PubMed  CAS  Article  Google Scholar 

  • Nielsen P, Fischer R, Buggisch P, Janka-Schaub G (2003) Effective treatment of hereditary haemochromatosis with desferrioxamine in selected cases. Br J Haematol 123: 952

    PubMed  Article  Google Scholar 

  • Moirand R, Mortaji AM, Loreal O, Paillard F, Brissot P, Deugnier Y (1997) A new syndrome of liver iron overload with normal transferrin saturation. Lancet 349: 95

    PubMed  CAS  Article  Google Scholar 

  • Mendler MH, Turlin B, Moirand R, Jouanolle AM, Sapey T, Guyader D, et al (1999) Insulin resistance-associated hepatic iron overload. Gastroenterology 117: 1155

    PubMed  CAS  Article  Google Scholar 

  • McNamara L, Gordeuk VR, MacPhail AP (2005) Ferroportin (Q248H) mutations in African families with dietary iron overload. J Gastroenterol Hepatol 20: 1855

    PubMed  CAS  Article  Google Scholar 

  • Gordeuk V, Mukiibi J, Hasstedt SJ, Samowitz W, Edwards CQ, West G, et al (1992) Iron overload in Africa. Interaction between a gene and dietary iron content. N Engl J Med 326: 95

    PubMed  CAS  Article  Google Scholar 

  • Gordeuk VR, Caleffi A, Corradini E, Ferrara F, Jones RA, Castro O, et al (2003) Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene. Blood Cells Mol Dis 31: 299

    PubMed  CAS  Article  Google Scholar 

  • Bonkovsky HL, Troy N, McNeal K, Banner BF, Sharma A, Obando J, et al (2002) Iron and HFE or TfR1 mutations as comorbid factors for development and progression of chronic hepatitis C. J Hepatol 37: 848

    PubMed  CAS  Article  Google Scholar 

  • Weiss G, Wachter H, Fuchs D (1995) Linkage of cellmediated immunity to iron metabolism. Immunol Today 16: 495

    PubMed  CAS  Article  Google Scholar 

  • Oexle H, Kaser A, Most J, Bellmann-Weiler R, Werner ER, Werner-Felmayer G, et al (2003) Pathways for the regulation of interferon-gamma-inducible genes by iron in human monocytic cells. J Leukoc Biol 74: 287

    PubMed  CAS  Article  Google Scholar 

  • Weiss G, Fuchs D, Hausen A, Reibnegger G, Werner ER, Werner-Felmayer G, et al (1992) Iron modulates interferon-gamma effects in the human myelomonocytic cell line THP-1. Exp Hematol 20: 605

    PubMed  CAS  Google Scholar 

  • Weiss G, Werner-Felmayer G, Werner ER, Grunewald K, Wachter H, Hentze MW (1994) Iron regulates nitric oxide synthase activity by controlling nuclear transcription. J Exp Med 180: 969

    PubMed  CAS  Article  Google Scholar 

  • Bird CL, Witte JS, Swendseid ME, Shikany JM, Hunt IF, Frankl HD, et al (1996) Plasma ferritin, iron intake, and the risk of colorectal polyps. Am J Epidemiol 144: 34

    PubMed  CAS  Google Scholar 

  • Huang X (2003) Iron overload and its association with cancer risk in humans: evidence for iron as a carcinogenic metal. Mutat Res 533: 153

    PubMed  CAS  Google Scholar 

  • Shaheen NJ, Silverman LM, Keku T, Lawrence LB, Rohlfs EM, Martin CF, et al (2003) Association between hemochromatosis (HFE) gene mutation carrier status and the risk of colon cancer. J Natl Cancer Inst 95: 154

    PubMed  CAS  Article  Google Scholar 

  • Hellerbrand C, Poppl A, Hartmann A, Scholmerich J, Lock G (2003) HFE C282Y heterozygosity in hepatocellular carcinoma: evidence for an increased prevalence. Clin Gastroenterol Hepatol 1: 279

    PubMed  CAS  Article  Google Scholar 

  • Fracanzani AL, Conte D, Fraquelli M, Taioli E, Mattioli M, Losco A, et al (2001) Increased cancer risk in a cohort of 230 patients with hereditary hemochromatosis in comparison to matched control patients with non-iron-related chronic liver disease. Hepatology 33: 647

    PubMed  CAS  Article  Google Scholar 

  • Wang SC, Lin KH, Chern JP, Lu MY, Jou ST, Lin DT, et al (2003) Severe bacterial infection in transfusion-dependent patients with thalassemia major. Clin Infect Dis 37: 984

    PubMed  Article  Google Scholar 

  • Cappellini MD, Cohen A, Piga A, Bejaoui M, Perrotta S, Agaoglu L, et al (2005) A Phase III study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with (beta)-thalassemia. Blood 107: 3455

    PubMed  Article  CAS  Google Scholar 

  • Hershko C, Hoffbrand AV, Keret D, Souroujon M, Maschler I, Monselise Y, et al (2005) Role of autoimmune gastritis, Helicobacter pylori and celiac disease in refractory or unexplained iron deficiency anemia. Haematologica 90: 585

    PubMed  CAS  Google Scholar 

  • Weiss G (2002) Pathogenesis and treatment of anaemia of chronic disease. Blood Rev 16: 87

    PubMed  Article  Google Scholar 

  • Weiss G, Gordeuk VR (2005) Benefits and risks of iron therapy for chronic anaemias. Eur J Clin Invest 35 [Suppl 3]: 36

    PubMed  CAS  Article  Google Scholar 

  • Looker AC, Dallman PR, Carroll MD, Gunter EW, Johnson CL (1997) Prevalence of iron deficiency in the United States. Jama 277: 973

    PubMed  CAS  Article  Google Scholar 

  • Umbreit J (2005) Iron deficiency: a concise review. Am J Hematol 78: 225

    PubMed  CAS  Article  Google Scholar 

  • Schrier SD (2005) Treatment of anemia due to iron deficiency. UpToDate Edition 13.2 Vol 2005

  • Annibale B, Capurso G, Chistolini A, D'Ambra G, DiGiulio E, Monarca B, et al (2001) Gastrointestinal causes of refractory iron deficiency anemia in patients without gastrointestinal symptoms. Am J Med 111: 439

    PubMed  CAS  Article  Google Scholar 

  • James MW, Chen CM, Goddard WP, Scott BB, Goddard AF (2005) Risk factors for gastrointestinal malignancy in patients with iron-deficiency anaemia. Eur J Gastroenterol Hepatol 17: 1197

    PubMed  Article  Google Scholar 

  • Schrier SD (2005) Causes and diagnosis of anemia due to iron deficiency. UpToDate Edition 13.2 Vol 2005

  • Han AP, Yu C, Lu L, Fujiwara Y, Browne C, Chin G, et al (2001) Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency. Embo J 20: 6909

    PubMed  CAS  Article  Google Scholar 

  • Idjradinata P, Pollitt E (1993) Reversal of developmental delays in iron-deficient anaemic infants treated with iron. Lancet 341: 1

    PubMed  CAS  Article  Google Scholar 

  • Jacobs P, Wood L, Bird AR (2000) Erythrocytes: better tolerance of iron polymaltose complex compared with ferrous sulphate in the treatment of anaemia. Hematol 5: 77

    PubMed  CAS  Google Scholar 

  • Harvey RS, Reffitt DM, Doig LA, Meenan J, Ellis RD, Thompson RP, et al (1998) Ferric trimaltol corrects iron deficiency anaemia in patients intolerant of iron. Aliment Pharmacol Ther 12: 845

    PubMed  CAS  Article  Google Scholar 

  • Nissenson AR, Berns JS, Sakiewicz P, Ghaddar S, Moore GM, Schleicher RB, et al (2003) Clinical evaluation of heme iron polypeptide: sustaining a response to rHuEPO in hemodialysis patients. Am J Kidney Dis 42: 325

    PubMed  CAS  Article  Google Scholar 

  • Annibale B, Marignani M, Monarca B, Antonelli G, Marcheggiano A, Martino G, et al (1999) Reversal of iron deficiency anemia after helicobacter pylori eradication in patients with asymptomatic gastritis. Ann Intern Med 131: 668

    PubMed  CAS  Google Scholar 

  • DuBois S, Kearney DJ (2005) Iron-deficiency anemia and helicobacter pylori infection: a review of the evidence. Am J Gastroenterol 100: 453

    PubMed  Article  Google Scholar 

  • Afzali B, Goldsmith DJ (2004) Intravenous iron therapy in renal failure: friend and foe? J Nephrol 17: 487

    PubMed  CAS  Google Scholar 

  • Steurer M, Wagner H, Gastl G (2004) Prevalence and management of anaemia in haematologic cancer patients receiving cyclic nonplatinum chemotherapy: results of a prospective national chart survey. Wien Klin Wochenschr 116: 367

    PubMed  Article  Google Scholar 

  • Roy CN, Andrews NC (2005) Anemia of inflammation: the hepcidin link. Curr Opin Hematol 12: 107

    PubMed  CAS  Article  Google Scholar 

  • Ludwiczek S, Aigner E, Theurl I, Weiss G (2003) Cytokine-mediated regulation of iron transport in human monocytic cells. Blood 101: 4148

    PubMed  CAS  Article  Google Scholar 

  • Tilg H, Ulmer H, Kaser A, Weiss G (2002) Role of IL-10 for induction of anemia during inflammation. J Immunol 169: 2204

    PubMed  CAS  Google Scholar 

  • Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T (2003) Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood 101: 2461

    PubMed  CAS  Article  Google Scholar 

  • Liu XB, Nguyen NB, Marquess KD, Yang F, Haile DJ (2005) Regulation of hepcidin and ferroportin expression by lipopolysaccharide in splenic macrophages. Blood Cells Mol Dis 35: 47

    PubMed  CAS  Article  Google Scholar 

  • Lee P, Peng H, Gelbart T, Wang L, Beutler E (2005) Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc Natl Acad Sci USA 102: 1906

    PubMed  CAS  Article  Google Scholar 

  • Lee P, Peng H, Gelbart T, Beutler E (2004) The IL-6- and lipopolysaccharide-induced transcription of hepcidin in HFE-, transferrin receptor 2-, and beta 2-microglobulindeficient hepatocytes. Proc Natl Acad Sci USA 101: 9263

    PubMed  CAS  Article  Google Scholar 

  • Macdougall IC, Cooper AC (2005) Hyporesponsiveness to erythropoietic therapy due to chronic inflammation. Eur J Clin Invest 35 [Suppl 3]: 32

    PubMed  CAS  Article  Google Scholar 

  • Theurl I, Mattle V, Seifert M, Mariani M, Marth C, Weiss G (2006) Dysregulated monocyte iron homeostasis and erythropoeitin formation in patients with anemia of chronic disease. Blood 107: 4142

    PubMed  CAS  Article  Google Scholar 

  • Punnonen K, Irjala K, Rajamaki A (1997) Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood 89: 1052

    PubMed  CAS  Google Scholar 

  • Horl WH, Holzer H, Mayer GJ (2002) Treatment of renal anemia with darbepoetin alfa: results of an Austrian multicenter study. Wien Klin Wochenschr 114: 967

    PubMed  Google Scholar 

  • Weiss GVRG, Hershko C (2005) Anemia of chronic disease. In: Cheson BD (ed) Basic and clinical oncology, Vol 30. CRC Press, Taylor & Francis Group, Boca Raton

    Google Scholar 

  • Eschbach JW (2002) Anemia management in chronic kidney disease: role of factors affecting epoetin responsiveness. J Am Soc Nephrol 13: 1412

    PubMed  Article  Google Scholar 

  • Eckardt KU (2001) Anemia in critical illness. Wien Klin Wochenschr 113: 84

    PubMed  CAS  Google Scholar 

  • Walsh TS, Lee RJ, Maciver CR, Garrioch M, Mackirdy F, Binning AR, et al (2006) Anemia during and at discharge from intensive care: the impact of restrictive blood transfusion practice. Intensive Care Med 32: 100

    PubMed  Article  Google Scholar 

  • Vincent JL, Baron JF, Reinhart K, Gattinoni L, Thijs L, Webb A, et al (2002) Anemia and blood transfusion in critically ill patients. Jama 288: 1499

    PubMed  Article  Google Scholar 

  • Corwin HL, Gettinger A, Pearl RG, Fink MP, Levy MM, Abraham E, et al (2004) The CRIT Study: Anemia and blood transfusion in the critically ill – current clinical practice in the United States. Crit Care Med 32: 39

    PubMed  Article  Google Scholar 

  • Munoz M, Romero A, Morales M, Campos A, Garcia-Erce JA, Ramirez G (2005) Iron metabolism, inflammation and anemia in critically ill patients. A cross-sectional study. Nutr Hosp 20: 115

    PubMed  CAS  Google Scholar 

  • Rogiers P, Zhang H, Leeman M, Nagler J, Neels H, Melot C, et al (1997) Erythropoietin response is blunted in critically ill patients. Intensive Care Med 23: 159

    PubMed  CAS  Article  Google Scholar 

  • Scharte M, Fink MP (2003) Red blood cell physiology in critical illness. Crit Care Med 31: S651

    PubMed  CAS  Article  Google Scholar 

  • Hobisch-Hagen P, Wiedermann F, Mayr A, Fries D, Jelkmann W, Fuchs D, et al (2001) Blunted erythropoietic response to anemia in multiply traumatized patients. Crit Care Med 29: 743

    PubMed  CAS  Article  Google Scholar 

  • La Ferla K, Reimann C, Jelkmann W, Hellwig-Burgel T (2002) Inhibition of erythropoietin gene expression signaling involves the transcription factors GATA-2 and NF-kappaB. Faseb J 16: 1811

    PubMed  CAS  Google Scholar 

  • Dybedal I, Jacobsen SE (1995) Transforming growth factor beta (TGF-beta), a potent inhibitor of erythropoiesis: neutralizing TGF-beta antibodies show erythropoietin as a potent stimulator of murine burst-forming unit erythroid colony formation in the absence of a burst-promoting activity. Blood 86: 949

    PubMed  CAS  Google Scholar 

  • Johnson CS, Keckler DJ, Topper MI, Braunschweiger PG, Furmanski P (1989) In vivo hematopoietic effects of recombinant interleukin-1 alpha in mice: stimulation of granulocytic, monocytic, megakaryocytic, and early erythroid progenitors, suppression of late-stage erythropoiesis, and reversal of erythroid suppression with erythropoietin. Blood 73: 678

    PubMed  CAS  Google Scholar 

  • Wang CQ, Udupa KB, Lipschitz DA (1995) Interferongamma exerts its negative regulatory effect primarily on the earliest stages of murine erythroid progenitor cell development. J Cell Physiol 162: 134

    PubMed  CAS  Article  Google Scholar 

  • Baskurt OK, Gelmont D, Meiselman HJ (1998) Red blood cell deformability in sepsis. Am J Respir Crit Care Med 157: 421

    PubMed  CAS  Google Scholar 

  • du Cheyron D, Parienti JJ, Fekih-Hassen M, Daubin C, Charbonneau P (2005) Impact of anemia on outcome in critically ill patients with severe acute renal failure. Intensive Care Med 31: 1529

    PubMed  Article  Google Scholar 

  • Sabatine MS, Morrow DA, Giugliano RP, Burton PB, Murphy SA, McCabe CH, et al (2005) Association of hemoglobin levels with clinical outcomes in acute coronary syndromes. Circulation 111: 2042

    PubMed  CAS  Article  Google Scholar 

  • Keough-Ryan TM, Kiberd BA, Dipchand CS, Cox JL, Rose CL, Thompson KJ, et al (2005) Outcomes of acute coronary syndrome in a large Canadian cohort: impact of chronic renal insufficiency, cardiac interventions, and anemia. Am J Kidney Dis 46: 845

    PubMed  Article  Google Scholar 

  • Wu WC, Rathore SS, Wang Y, Radford MJ, Krumholz HM (2001) Blood transfusion in elderly patients with acute myocardial infarction. N Engl J Med 345: 1230

    PubMed  CAS  Article  Google Scholar 

  • Toy P, Popovsky MA, Abraham E, Ambruso DR, Holness LG, Kopko PM, et al (2005) Transfusion-related acute lung injury: definition and review. Crit Care Med 33: 721

    PubMed  Article  Google Scholar 

  • Carson JL, Altman DG, Duff A, Noveck H, Weinstein MP, Sonnenberg FA, et al (1999) Risk of bacterial infection associated with allogeneic blood transfusion among patients undergoing hip fracture repair. Transfusion 39: 694

    PubMed  CAS  Article  Google Scholar 

  • Heiss MM, Mempel W, Delanoff C, Jauch KW, Gabka C, Mempel M, et al (1994) Blood transfusion-modulated tumor recurrence: first results of a randomized study of autologous versus allogeneic blood transfusion in colorectal cancer surgery. J Clin Oncol 12: 1859

    PubMed  CAS  Google Scholar 

  • Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, et al (1999) A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 340: 409

    PubMed  CAS  Article  Google Scholar 

  • Corwin HL, Gettinger A, Pearl RG, Fink MP, Levy MM, Shapiro MJ, et al (2002) Efficacy of recombinant human erythropoietin in critically ill patients: a randomized controlled trial. Jama 288: 2827

    PubMed  CAS  Article  Google Scholar 

  • Silverberg DS, Wexler D, Blum M, Iaina A, Sheps D, Keren G, et al (2005) Effects of treatment with epoetin beta on outcomes in patients with anaemia and chronic heart failure. Kidney Blood Press Res 28: 41

    PubMed  CAS  Article  Google Scholar 

  • Kosch M, Schaefer RM (2003) Indications and practical management of parenteral iron therapy. Wien Klin Wochenschr 115: 380

    PubMed  Google Scholar 

  • Atkinson PG, Blackwell JM, Barton CH (1997) Nramp1 locus encodes a 65 kDa interferon-gamma-inducible protein in murine macrophages. Biochem J 325: 779

    PubMed  CAS  Google Scholar 

  • Fritsche G, Dlaska M, Barton H, Theurl I, Garimorth K, Weiss G (2003) Nramp1 functionality increases inducible nitric oxide synthase transcription via stimulation of IFN regulatory factor 1 expression. J Immunol 171: 1994

    PubMed  CAS  Google Scholar 

  • Shaw GC, Cope JJ, Li L, Corson K, Hersey C, Ackermann GE, et al (2006) Mitoferrin is essential for erythroid iron assimilation. Nature 440: 96

    PubMed  CAS  Article  Google Scholar 

  • Oudit GY, Sun H, Trivieri MG, Koch SE, Dawood F, Ackerley C, et al (2003) L-type Ca2+ channels provide a major pathway for iron entry into cardiomyocytes in ironoverload cardiomyopathy. Nat Med 9: 1187

    PubMed  CAS  Article  Google Scholar 

  • Chen H, Attieh ZK, Su T, Syed BA, Gao H, Alaeddine RM, et al (2004) Hephaestin is a ferroxidase that maintains partial activity in sex-linked anemia mice. Blood 103: 3933

    PubMed  CAS  Article  Google Scholar 

  • Donovan A, Brownlie A, Zhou Y, Shepard J, Pratt SJ, Moynihan J, et al (2000) Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature 403: 776

    PubMed  CAS  Article  Google Scholar 

  • Feder JN (1999) The hereditary hemochromatosis gene (HFE): a MHC class I-like gene that functions in the regulation of iron homeostasis. Immunol Res 20: 175

    PubMed  CAS  Google Scholar 

  • Fleming MD, Trenor CC 3rd, Su MA, Foernzler D, Beier DR, Dietrich WF, et al (1997) Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat Genet 16: 383

    PubMed  CAS  Google Scholar 

  • Fleming RE, Bacon BR (2005) Orchestration of iron homeostasis. N Engl J Med 352: 1741

    PubMed  CAS  Article  Google Scholar 

  • Gunshin H, Starr CN, Direnzo C, Fleming MD, Jin J, Greer EL, et al (2005) Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in mice. Blood 106: 2879

    PubMed  CAS  Article  Google Scholar 

  • McKie AT, Marciani P, Rolfs A, Brennan K, Wehr K, Barrow D, et al (2000) A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell 5: 299

    PubMed  CAS  Article  Google Scholar 

  • Schaer DJ, Schaer CA, Buehler PW, Boykins RA, Schoedon G, Alayash AI, et al (2006) CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin. Blood 107: 373

    PubMed  CAS  Article  Google Scholar 

  • Theil EC (2003) Ferritin: at the crossroads of iron and oxygen metabolism. J Nutr 133: 1549S

    PubMed  CAS  Google Scholar 

  • Anderson GJ, Frazer DM, McKie AT, Vulpe CD, Smith A (2005) Mechanisms of haem and non-haem iron absorption: lessons from inherited disorders of iron metabolism. Biometals 18: 339

    PubMed  CAS  Article  Google Scholar 

  • Knutson M, Wessling-Resnick M (2003) Iron metabolism in the reticuloendothelial system. Crit Rev Biochem Mol Biol 38: 61

    PubMed  CAS  Google Scholar 

  • Ludwiczek S, Theurl I, Artner-Dworzak E, Chorney M, Weiss G (2004) Duodenal HFE expression and hepcidin levels determine body iron homeostasis: modulation by genetic diversity and dietary iron availability. J Mol Med 82: 373

    PubMed  CAS  Article  Google Scholar 

  • Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, et al (2005) Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemiareperfusion injury. J Clin Invest 115: 610

    PubMed  CAS  Article  Google Scholar 

  • Whitington PF, Malladi P (2005) Neonatal hemochromatosis: is it an alloimmune disease? J Pediatr Gastroenterol Nutr 40: 544

    PubMed  Article  Google Scholar 

  • Ponka P (2002) Rare causes of hereditary iron overload. Semin Hematol 39: 249

    PubMed  CAS  Article  Google Scholar 

  • Kawashima A, Oda Y, Yachie A, Koizumi S, Nakanishi I (2002) Heme oxygenase-1 deficiency: the first autopsy case. Hum Pathol 33: 125

    PubMed  Article  Google Scholar 

  • Kato J, Fujikawa K, Kanda M, Fukuda N, Sasaki K, Takayama T, et al (2001) A mutation, in the iron-responsive element of H ferritin mRNA, causing autosomal dominant iron overload. Am J Hum Genet 69: 191

    PubMed  CAS  Article  Google Scholar 

  • Mims MP, Guan Y, Pospisilova D, Priwitzerova M, Indrak K, Ponka P, et al (2005) Identification of a human mutation of DMT1 in a patient with microcytic anemia and iron overload. Blood 105: 1337

    PubMed  CAS  Article  Google Scholar 

  • Beaumont C, Delaunay J, Hetet G, Grandchamp B, de Montalembert M, Tchernia G (2006) Two new human DMT1 gene mutations in a patient with microcytic anemia, low ferritinemia, and liver iron overload. Blood 107: 4168

    PubMed  CAS  Article  Google Scholar 

  • Iolascon A, d'Apolito M, Servedio V, Cimmino F, Piga A, Camaschella C (2006) Microcytic anemia and hepatic iron overload in a child with compound heterozygous mutations in DMT1 (SCL11A2). Blood 107: 349

    PubMed  CAS  Article  Google Scholar 

  • Miyajima H (2003) Aceruloplasminemia, an iron metabolic disorder. Neuropathology 23: 345

    PubMed  Article  Google Scholar 

  • Bacon BR, Powell LW, Adams PC, Kresina TF, Hoofnagle JH (1999) Molecular medicine and hemochromatosis: at the crossroads. Gastroenterology 116: 193

    PubMed  CAS  Article  Google Scholar 

  • Adams PC, Deugnier Y, Moirand R, Brissot P (1997) The relationship between iron overload, clinical symptoms, and age in 410 patients with genetic hemochromatosis. Hepatology 25: 162

    PubMed  CAS  Google Scholar 

  • Adams PC, Chakrabarti S (1998) Genotypic/phenotypic correlations in genetic hemochromatosis: evolution of diagnostic criteria. Gastroenterology 114: 319

    PubMed  CAS  Article  Google Scholar 

  • Niederau C, Fischer R, Purschel A, Stremmel W, Haussinger D, Strohmeyer G (1996) Long-term survival in patients with hereditary hemochromatosis. Gastroenterology 110: 1107

    PubMed  CAS  Article  Google Scholar 

  • Wojcik JP, Speechley MR, Kertesz AE, Chakrabarti S, Adams PC (2002) Natural history of C282Y homozygotes for hemochromatosis. Can J Gastroenterol 16: 297

    PubMed  Google Scholar 

  • Evens AM, Mehta J, Gordon LI (2004) Rust and corrosion in hematopoietic stem cell transplantation: the problem of iron and oxidative stress. Bone Marrow Transplant 34: 561

    PubMed  CAS  Article  Google Scholar 

  • Fargion S (1999) Dysmetabolic iron overload syndrome. Haematologica 84: 97

    PubMed  CAS  Article  Google Scholar 

  • Rund D, Rachmilewitz E (2005) Beta-thalassemia. N Engl J Med 353: 1135

    PubMed  CAS  Article  Google Scholar 

  • Larrick JW, Hyman ES (1984) Acquired iron-deficiency anemia caused by an antibody against the transferrin receptor. N Engl J Med 311: 214

    PubMed  CAS  Article  Google Scholar 

Download references

Author information

Affiliations

  1. Klinische Abteilung für Allgemeine Innere Medizin, Klinische Infektiologie und Immunologie, Medizinische Universität Innsbruck, Innsbruck, Austria

    Manfred Nairz & Günter Weiss

Authors
  1. Manfred Nairz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Günter Weiss
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Günter Weiss.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Nairz, M., Weiss, G. Molecular and clinical aspects of iron homeostasis: from anemia to hemochromatosis. Wien Klin Wochenschr 118, 442–462 (2006). https://doi.org/10.1007/s00508-006-0653-7

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00508-006-0653-7

Keywords

  • Hemochromatosis
  • Secondary iron overload
  • Anemia of chronic disease
  • Anemia of critical illness
  • Iron deficiency