title: Lipopolysaccharide evokes resistance to erythropoiesis induced by the long-acting erythropoietin analogue darbepoetin alfa in rats.
abstract: BACKGROUND
  Anemia is common in patients with sepsis but its mechanism is unknown. We tested the hypothesis that effects on erythropoiesis evoked by darbepoetin alfa (DA), a long-acting erythropoietin analog, are diminished by lipopolysaccharide (LPS).
  
  
  METHODS
  We performed a prospective, controlled, randomized animal study (male Lewis rats n = 44). The interventions we used were intraperitoneal injection of Escherichia coli LPS (10 mg/kg) or vehicle followed by either DA (25 microg/kg) or vehicle (four experimental groups). Blood and reticulocyte counts and variables of iron metabolism were measured at baseline and 3 and 14 days after interventions.
  
  
  RESULTS
  Animals treated with DA alone showed an eightfold increase in reticulocyte count from baseline on Day 3, whereas no increase was seen in animals administered LPS or LPS/DA. On Day 14, the red blood cell count and hemoglobin concentration had increased by approximately 10% from baseline (P < 0.001) in the DA group but had decreased after LPS on Days 3 and 14 (P < 0.05) and in animals administered LPS/DA. Consumption of iron was seen on Day 3 in the DA group but not after LPS or LPS/DA combined. Values of ferritin and transferrin did not change between groups.
  
  
  CONCLUSIONS
  LPS abolishes erythropoiesis and iron use evoked by DA and this is accompanied by a decrease in hemoglobin concentration and red blood cell concentration. Accordingly, endotoxin suppresses DAs ability to increase erythropoiesis.
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen, Essen, Germany. Peter.Brendt@uni-duisburg-essen.de
authors.forename: Peter
authors.initials: P
authors.lastname: Brendt
authors.forename: Ariane
authors.initials: A
authors.lastname: Horwat
authors.forename: Simon T
authors.initials: ST
authors.lastname: Schäfer
authors.forename: Sven C
authors.initials: SC
authors.lastname: Dreyer
authors.forename: Joachim
authors.initials: J
authors.lastname: Göthert
authors.forename: Jürgen
authors.initials: J
authors.lastname: Peters
mesh_terms: D000740:Anemia / Q000209:etiology; D000818:Animals; D000068256:Darbepoetin alfa; D004912:Erythrocytes / Q000378:metabolism; D004920:Erythropoiesis; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism; D006397:Hematinics / Q000494:pharmacology; D007362:Intensive Care Units; D008070:Lipopolysaccharides / Q000378:metabolism*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D012156:Reticulocytes / Q000378:metabolism; D013997:Time Factors
chemical_list: D006397:Hematinics; D008070:Lipopolysaccharides; D004921:Erythropoietin; D000068256:Darbepoetin alfa