title: Inflammation-induced hepcidin-25 is associated with the development of anemia in septic patients: an observational study.
abstract: BACKGROUND
  Anemia is a frequently encountered problem during inflammation. Hepcidin is an interleukin-6 (IL-6)-induced key modulator of inflammation-associated anemia. Human sepsis is a prototypical inflammatory syndrome, often complicated by the development of anemia. However, the association between inflammation, hepcidin release and anemia has not been demonstrated in this group of patients. Therefore, we explored the association between hepcidin and sepsis-associated anemia.
  
  
  METHODS
  92 consecutive patients were enrolled after presentation on the emergency ward of a university hospital with sepsis, indicated by the presence of a proven or suspected infection and ≥ 2 extended systemic inflammatory response syndrome (SIRS) criteria. Blood was drawn at day 1, 2 and 3 after admission for the measurement of IL-6 and hepcidin-25. IL-6 levels were correlated with hepcidin concentrations. Hemoglobin levels and data of blood transfusions during 14 days after hospitalisation were retrieved and the rate of hemoglobin decrease was correlated to hepcidin levels.
  
  
  RESULTS
  53 men and 39 women with a mean age of 53.3 ± 1.8 yrs were included. Hepcidin levels were highest at admission (median[IQR]): 17.9[10.1 to 28.4]nmol/l and decreased to normal levels in most patients within 3 days (9.5[3.4 to 17.9]nmol/l). Hepcidin levels increased with the number of extended SIRS criteria (P = 0.0005). Highest IL-6 levels were measured at admission (125.0[46.3 to 330.0]pg/ml) and log-transformed IL-6 levels significantly correlated with hepcidin levels at admission (r = 0.28, P = 0.015), day 2 (r = 0.51, P < 0.0001) and day 3 (r = 0.46, P < 0.0001). Twelve patients received one or more blood transfusions during the first 2 weeks of admission, not related to active bleeding. These patients had borderline significant higher hepcidin level at admission compared to non-transfused patients (26.9[17.2 to 53.9] vs 17.9[9.9 to 28.8]nmol/l, P = 0.052). IL-6 concentrations did not differ between both groups. Correlation analyses showed significant associations between hepcidin levels on day 2 and 3 and the rate of decrease in hemoglobin (Spearman's r ranging from -0.32, P = 0.03 to -0.37, P = 0.016, respectively).
  
  
  CONCLUSIONS
  These data suggest that hepcidin-25 may be an important modulator of anemia in septic patients with systemic inflammation.
authors.affiliation: Department of Intensive Care Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Geert Grooteplein-Zuid 10, PO Box 9201, 6500 HB Nijmegen, The Netherlands.
authors.forename: Lucas T
authors.initials: LT
authors.lastname: van Eijk
authors.forename: Joyce J C
authors.initials: JJ
authors.lastname: Kroot
authors.forename: Mirjam
authors.initials: M
authors.lastname: Tromp
authors.forename: Johannes G
authors.initials: JG
authors.lastname: van der Hoeven
authors.forename: Dorine W
authors.initials: DW
authors.lastname: Swinkels
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
mesh_terms: D000740:Anemia / Q000209:etiology*; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D001803:Blood Transfusion / Q000706:statistics & numerical data; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D064451:Hepcidins; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000150:complications* / Q000628:therapy
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D006454:Hemoglobins; D064451:Hepcidins; D015850:Interleukin-6