title: Systemic inflammation up-regulates serum hepcidin in exacerbations and stabile chronic obstructive pulmonary disease.
abstract: OBJECTIVE
  Hepcidin is the main regulator of systemic iron homeostasis and its expression is modulated by iron status, hypoxia, erythroid factors and inflammation. The aim of our study was to examine a relationship between level of hepcidin and iron status, erythropoietic activity, hypoxia and inflammation in exacerbations and stable COPD patients. We hypothesized that hepcidin concentration is changed in COPD patients and is substantially influenced by inflammation and/or hypoxia.
  
  
  METHODS
  The study included 40 COPD patients and 30 healthy subjects. We measured haemoglobin, serum level of hepcidin and parameters indicative for inflammation: interleukin-6 (IL-6) and C reactive protein (CRP); hypoxia: partial oxygen pressure and haemoglobin oxygen saturation; iron status: iron, total iron binding capacity (TIBC), transferring saturation and ferritin; and erythropoietic activity: soluble transferrin receptors, reticulocytes, and erythropoietin.
  
  
  RESULTS
  Hepcidin was elevated in exacerbations and in a stable phase compared to the control group and we found positive correlations of hepcidin with inflammatory markers IL-6 and CRP. Hepcidin also correlated positively with ferritin and inversely with TIBC. However, in COPD patients reticulocyte count was significantly reduced and negative correlation with hepcidin was established in exacerbation. No correlations were observed with iron, or indices of hypoxia. In the control group, positive associations were observed only with indices of iron status, positive with ferritin and negative one with TIBC.
  
  
  CONCLUSIONS
  Systemic inflammation and elevated values of IL-6 present in exacerbations and stabile COPD might be responsible for the observed increased hepcidin level.
authors.affiliation: Department of Medical Laboratory Diagnosis, University Hospital Center Split, 21000 Split, Croatia. Electronic address: leida.tandara@gmail.com.
authors.forename: Leida
authors.initials: L
authors.lastname: Tandara
authors.affiliation: Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia. Electronic address: tihana_zanic@yahoo.co.uk.
authors.forename: Tihana Zanic
authors.initials: TZ
authors.lastname: Grubisic
authors.affiliation: Clinical Department for Pulmonary Diseases, Universiti Hospital Center Split, 21000 Split, Croatia. Electronic address: ivan.gudelj.1956@gmail.com.
authors.forename: Gudelj
authors.initials: G
authors.lastname: Ivan
authors.affiliation: Department of Cardiology, University Hospital Center Split, 21000 Split, Croatia. Electronic address: zrinkacn@gmail.com.
authors.forename: Zrinka
authors.initials: Z
authors.lastname: Jurisic
authors.affiliation: Department of Human Reproduction, Clinic for Women's Diseases and Obstetrics, University Hospital Center Split, 21000 Split, Croatia. Electronic address: marijan.tandara@inet.hr.
authors.forename: Marijan
authors.initials: M
authors.lastname: Tandara
authors.affiliation: Department of Medical Laboratory Diagnosis, University Hospital Center Split, 21000 Split, Croatia. Electronic address: katarina.gugo@gmail.com.
authors.forename: Katarina
authors.initials: K
authors.lastname: Gugo
authors.affiliation: Clinical Department for Pulmonary Diseases, Universiti Hospital Center Split, 21000 Split, Croatia. Electronic address: suzana.mladinov@gmail.com.
authors.forename: Suzana
authors.initials: S
authors.lastname: Mladinov
authors.affiliation: Department of Medical Laboratory Diagnosis, University Hospital Center Split, 21000 Split, Croatia. Electronic address: ilza.salamunic@gmail.com.
authors.forename: Ilza
authors.initials: I
authors.lastname: Salamunic
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D018450:Disease Progression; D004921:Erythropoietin / Q000097:blood / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006454:Hemoglobins / Q000378:metabolism; D064451:Hepcidins / Q000097:blood / Q000235:genetics*; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D007501:Iron / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D011990:Receptors, Transferrin / Q000097:blood / Q000235:genetics; D012156:Reticulocytes / Q000378:metabolism / Q000473:pathology; D014168:Transferrin / Q000235:genetics / Q000378:metabolism
chemical_list: C554270:EPO protein, human; C578702:HAMP protein, human; D006454:Hemoglobins; D064451:Hepcidins; C508600:IL6 protein, human; D015850:Interleukin-6; D011990:Receptors, Transferrin; D014168:Transferrin; D004921:Erythropoietin; D002097:C-Reactive Protein; D007501:Iron; D010100:Oxygen
keywords: COPD; Hepcidin; Interleukin-6; Iron metabolism; Systemic inflammation