Systemic inflammation up-regulates serum hepcidin in exacerbations and stabile chronic obstructive pulmonary disease

Clinical Biochemistry

Volumn 48, Issue 18, 2015, Pages 1252-1257

  Tandara, Leida ^a   Grubisic, Tihana Zanic ^b   Ivan, Gudelj ^a   Jurisic, Zrinka ^a   Tandara, Marijan ^a   Gugo, Katarina ^a   Mladinov, Suzana ^a   Salamunic, Ilza ^a  

^a UNIVERSITY HOSPITAL SPLIT   (Croatia)

^b UNIVERSITY OF ZAGREB   (Croatia)

Author keywords

COPD; Hepcidin; Interleukin 6; Iron metabolism; Systemic inflammation

Indexed keywords

C REACTIVE PROTEIN; ERYTHROPOIETIN; FERRITIN; HEMOGLOBIN; HEPCIDIN; INTERLEUKIN 6; IRON; TRANSFERRIN; TRANSFERRIN RECEPTOR; EPO PROTEIN, HUMAN; HAMP PROTEIN, HUMAN; IL6 PROTEIN, HUMAN; OXYGEN;

AGED; ARTICLE; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL ARTICLE; CONTROLLED STUDY; DISEASE EXACERBATION; ERYTHROPOIESIS; FEMALE; HEMATOLOGICAL PARAMETERS; HEMOGLOBIN BLOOD LEVEL; HOMEOSTASIS; HUMAN; HYPOXIA; INFLAMMATION; IRON BALANCE; IRON BINDING CAPACITY; MALE; OXYGEN SATURATION; OXYGEN TENSION; PRIORITY JOURNAL; PROTEIN EXPRESSION; RETICULOCYTE COUNT; UPREGULATION; ANOXIA; BLOOD; CASE CONTROL STUDY; DISEASE COURSE; GENE EXPRESSION; GENETICS; METABOLISM; MIDDLE AGED; PATHOLOGY; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; RETICULOCYTE; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ANOXIA; C-REACTIVE PROTEIN; CASE-CONTROL STUDIES; DISEASE PROGRESSION; ERYTHROPOIETIN; FEMALE; GENE EXPRESSION; HEMOGLOBINS; HEPCIDINS; HUMANS; INFLAMMATION; INTERLEUKIN-6; IRON; MALE; MIDDLE AGED; OXYGEN; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; RECEPTORS, TRANSFERRIN; RETICULOCYTES; TRANSFERRIN;

EID: 84949097160     PISSN: 00099120     EISSN: 18732933     Source Type: Journal    
DOI: 10.1016/j.clinbiochem.2015.07.010     Document Type: Article

References (37)

1. Ganz T., Nemeth E. Hepcidin and iron homeostasis. Biochim. Biophys. Acta 1823, 2012:1434-1443.
2. Kemna E.H., Kartikasari A.E., van Tits L.J., Pickkers P., Tjalsma H., Swinkels D.W. Regulation of hepcidin: insights from biochemical analyses on human serum samples. Blood Cells Mol. Dis. 2008, 40:339-346.
3. Nemeth E., Rivera S., Gabayan V., Keller C., Taudorf S., Pedersen B.K., et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J. Clin. Invest. 2004, 113:1271-1276.
4. Zhang A.S., Enns C.A. Molecular mechanisms of normal iron homeostasis. Hematology Am. Soc. Hematol. Educ. Program 2009, 207-214.
5. Nicolas G., Chauvet C., Viatte L., Danan J.L., Bigard X., Devaux I., et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J. Clin. Invest. 2002, 110:1037-1044.
6. Piperno A., Galimberti S., Mariani R., Pelucchi S., Ravasi G., Lombardi C., et al. Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in vivo: data from the HIGHCARE project. Blood 2011, 117:2953-2959.
7. Silverberg D.S., Mor R., Weu M.T., Schwartz D., Schwartz I.F., Chernin G. Anemia and iron deficiency in COPD patients: prevalence and the effects of correction of the anemia with erythropoiesis stimulating agents and intravenous iron. BMC Pulm. Med. 2014, 14:24.
8. Kollert F., Müller C., Tippelt A., Jörres R.A., Heidinger D., Probst C., et al. Anaemia in chronic respiratory failure. Int. J. Clin. Pract. 2011, 65:479-486.
9. Schneckenpointner R., Jörres R.A., Meidenbauer N., Kollert F., Pfeifer M., Budweiser S. The clinical significance of anaemia and disturbed iron homeostasis in chronic respiratory failure. Int. J. Clin. Pract. 2014, 68:130-138.
10. Similowski T., Agustí A., MacNee W., Schönhofer B. The potential impact of anaemia of chronic disease in COPD. Eur. Respir. J. 2006, 27:390-396.
11. Urban M., Burghuber O.C., Hübl W., Funk G.C. Iron deficiency in non-anemic patients with chronic obstructive pulmonary disease. Eur. Respir. J. 2011, 38:2937.
12. Rhodes C.J., Wharton J., Howard L., Gibbs J.S., Vonk-Noordegraaf A., Wilkins M.R. Iron deficiency in pulmonary arterial hypertension: a potential therapeutic target. Eur. Respir. J. 2011, 38:1453-1460.
13. Ruiter G., Lankhorst S., Boonstra A., Postmus P.E., Zweegman S., Westerhof N., van der Laarse W.J., Vonk-Noordegraaf A. Iron deficiency is common in idiopathic pulmonary arterial hypertension. Eur. Respir. J. 2011, 37:1386-1391.
14. Rhodes C.J., Howard L.S., Busbridge M., Ashby D., Kondili E., Gibbs J.S., et al. Hypertension, iron deficiency and raised hepcidin in idiopathic pulmonary arterial. J. Am. Coll. Cardiol. 2011, 58:300-309.
15. From the global strategy for the diagnosis, management and prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Available from:, (Date last updated January 2014. Accessed July 24th 2014). http://www.goldcopd.org/.
16. Celli B.R., MacNee W., ATS/ERS Task Force Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur. Respir. J. 2004, 23:932-946.
17. Markoulaki D., Kostikas K., Papatheodorou G., Koutsokera A., Alchanatis M., Bakakos P., et al. Hemoglobin, erythropoietin and systemic inflammation in exacerbations of chronic obstructive pulmonary disease. Eur. J. Intern. Med. 2011, 22:103-107.
18. 2-microglobulin-deficient hepatocytes. Proc. Natl. Acad. Sci. U. S. A. 2004, 25:9263-9265.
19. Nemeth E., Valore E.V., Territo M., Schiller G., Lichenstein A., Ganz T. Hepcidin, putative mediator of anemia of inflammation, is type II acute-phase protein. Blood 2003, 101:2461-2463.
20. Kemna E., Pickkers P., Nemeth E., van der Hoeven H., Swinkels D. Time course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. Blood 2005, 106:1864-1866.
21. Nguyen N.B., Callaghan K.D., Ghio A.J., Haile D.J., Yang F. Hepcidin expression and iron transport in alveolar macrophages. Am. J. Physiol. Lung Cell. Mol. Physiol. 2006, 291:L417-L425.
22. Frazier M.D., Mamo L.B., Ghio A.J., Turi J.L. Hepcidin expression in human airway epithelial cells is regulated by interferon-γ. Respir. Res. 2011, 12:100.
23. Sinden N.J., Stockley R.A. Systemic inflammation and comorbidity in COPD: a result of 'overspill' of inflammatory mediators from the lungs? Review of the evidence. Thorax 2010, 65:930-936.
24. Pak M., Lopez M.A., Gabayan V., Ganz T., Rivera S. Suppression of hepcidin during anemia requires erythropoietic activity. Blood 2006, 108:3730-3735.
25. Volke M., Gale D.P., Maegdefrau U., Schley G., Klanke B., Bosserhoff A.K., et al. Evidence for a lack of a direct transcriptional suppression of the iron regulatory peptide hepcidin by hypoxia-inducible factors. PLoS One 2009, 4:e7875.
26. Peyssonnaux C., Zinkernagel A.S., Schuepbach R.A., Rankin E., Vaulont S., Haase V.H., et al. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J. Clin. Invest. 2007, 117:1926-1932.
27. Sonnweber T., Nachbaur D., Schroll A., Nairz M., Seifert M., Demetz E., et al. Hypoxia induced downregulation of hepcidin is mediated by platelet derived growth factor BB. Gut 2014, 63:1951-1959.
28. Kroot J.J.C., Tjalsma H., Fleming R.E., Swinkels D.W. Hepcidin in human iron disorders: diagnostic implications. Clin. Chem. 2011, 57:1650-1669.
29. Duru S., Bilgin E., Ardic S. Hepcidin: a useful marker in chronic obstructive pulmonary disease. Ann. Thorac. Med. 2012, 7:31-35.
30. Gagliardo B., Kubat N., Faye A., Jaouen M., Durel B., Deschemin J.C., et al. Pro-hepcidin is unable to degrade the iron exporter ferroportin unless maturated by a furin-dependent process. J. Hepatol. 2009, 50:394-401.
31. Lin L., Valore E.V., Nemeth E., Goodnough J.B., Gabayan V., Ganz T. Iron transferrin regulates hepcidin synthesis in primary hepatocyte culture through hemojuvelin and BMP2/4. Blood 2007, 110(6):2182-2189.
32. Kitsati N., Liakos D., Ermeidi E., Mantzaris M.D., Vasakos S., Kyratzopoulou E. Rapid elevation of transferrin saturation and serum hepcidin concentration in hemodialysis patients after intravenous iron infusion. Haematologica 2015, e80-3.
33. McCranor B.J., Kim M.J., Cruz N.M., Xue Q.L., Berger A.E., Walston J.D., et al. Interleukin-6 directly impairs the erythroid development of human TF-1 erythroleukemic cells. Blood Cells Mol. Dis. 2014, 52:126-133.
34. Gardenghi S., Renaud T.M., Meloni A., Casu C., Crielaard B.J., Bystrom L.M., et al. Distinct roles for hepcidin and interleukin-6 in the recovery from anemia in mice injected with heat-killed Brucella abortus. Blood 2014, 123:1137-1145.
35. Dassler K., Zydek M., Wandzik K., Kaup M., Fuchs H. Release of the soluble transferrin receptor is directly regulated by binding of its ligand ferritransferrin. J. Biol. Chem. 2006, 281:3297-3304.
36. Busti F., Campostrini N., Martinelli N., Girelli D. Iron deficiency in the elderly population, revisited in the hepcidin era. Front. Pharmacol. 2014, 5:83.
37. Macdougall I.C., Malyszko J., Hider R.C., Bansal S.S. Current status of the measurement of blood hepcidin levels in chronic kidney disease. Clin. J. Am. Soc. Nephrol. 2010, 5:1681-1689.