title: Suppression of erythropoiesis in patients with chronic heart failure and anaemia of unknown origin: evidence of an immune basis.
abstract: OBJECTIVE
  Anaemia is a prevalent and adverse comorbidity in chronic heart failure (CHF) but its origins are frequently elusive. Diffuse inflammation is also prominent in CHF and a potent inhibitor of erythrocyte production. We tested the hypothesis that unexplained anaemia in CHF might be subsequent to diminished erythropoiesis as a result of an immune-mediated suppression of erythroid colony formation.
  
  
  METHODS
  We studied 61 CHF patients and 20 healthy control subjects. Circulating primitive haematopoietic (CD34(+)) and erythroid precursor cells were quantified by flow cytometry. Circulating erythroid progenitors (BFU-E) were cultured in methylcellulose in the presence and absence of monocytes and sera, and with anti-TNFα neutralising antibodies.
  
  
  RESULTS
  Despite higher erythropoietin levels, anaemic patients exhibited lower absolute reticulocyte counts and reticulocyte production indices (P<0.001) than non-anaemic patients and healthy controls. Diminished erythropoiesis was paralleled by attenuated circulating CD34(+), erythroid progenitor and precursor cells in anaemic patients (all P<0.01). Depletion of monocytes from cultures derived only from anaemic patients enhanced BFU-E growth (P=0.03). Only the addition of monocytes and sera from anaemic patients suppressed autologous or allogeneic BFU-E colony formation (P=0.02). Serum TNFα levels were highest in anaemic patients and anti-TNFα neutralising antibodies partly abrogated the inhibitory effects of anaemic sera on erythroid colony growth (P=0.03).
  
  
  CONCLUSIONS
  Unexplained anaemia in patients with CHF results partly from suppressed erythropoiesis and monocytes, via a direct effect of TNFα on erythroid cells, orchestrate a degree of this suppression.
authors.affiliation: Clinical Cardiology, National Heart & Lung Institute, Imperial College, London, UK. obiokonko@aol.com
authors.forename: Darlington O
authors.initials: DO
authors.lastname: Okonko
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Marley
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.forename: Philip A
authors.initials: PA
authors.lastname: Poole-Wilson
authors.forename: Myrtle Y
authors.initials: MY
authors.lastname: Gordon
mesh_terms: D000368:Aged; D000740:Anemia / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology*; D002478:Cells, Cultured; D002908:Chronic Disease; D004920:Erythropoiesis / Q000276:immunology*; D005260:Female; D006333:Heart Failure / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*