Lipopolysaccharide evokes resistance to erythropoiesis induced by the long-acting erythropoietin analogue darbepoetin alfa in rats.
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.
Brendt
Peter
P
Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen, Essen, Germany. Peter.Brendt@uni-duisburg-essen.de
Horwat
Ariane
A
Schäfer
Simon T
ST
Dreyer
Sven C
SC
Göthert
Joachim
J
Peters
Jürgen
J
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
D006397:Hematinics; D008070:Lipopolysaccharides; D004921:Erythropoietin; D000068256:Darbepoetin alfa