Erythropoietin augments the cytokine response to acute endotoxin-induced inflammation in humans.
Recent studies have shown that erythropoietin (EPO) offers protection against ischemia, hemorrhagic shock and systemic inflammation in many tissues and it has been suggested that EPO has anti-inflammatory effects. With the aim of investigating the potential acute anti-inflammatory effects of EPO in a human in vivo model of acute systemic low-grade inflammation, we measured circulating inflammatory mediators after intravenous administration of Escherichia coli endotoxin (LPS) bolus injection (0.1 ng/kg of body weight) in young healthy male subjects. The subjects were divided into three groups receiving either (1) LPS alone, (2) EPO alone (15,000 IE of rHuEPO) or (3) EPO and LPS. Endotoxin administration alone induced a 3-, 12- and 5-fold increase in plasma concentrations of TNF-alpha, IL-6 and IL-10, respectively, 3h after LPS challenge. When EPO was given prior to a bolus injection with endotoxin, the levels of TNF-alpha and IL-6 were enhanced by 5- and 40-fold, respectively, whereas the endotoxin-induced increase in IL-10 response was not influenced by EPO. In contrast to our hypothesis, we find that EPO augments the acute inflammatory effect.
Hojman
Pernille
P
Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Pernille.Hoejman.Moeller@rh.regionh.dk
Taudorf
Sarah
S
Lundby
Carsten
C
Pedersen
Bente Klarlund
BK
D000328:Adult; D016207:Cytokines / Q000276:immunology*; D004731:Endotoxins; D004921:Erythropoietin / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology*; D018836:Inflammation Mediators; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood; D018655:Lymphocyte Count; D008297:Male; D009504:Neutrophils; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016207:Cytokines; D004731:Endotoxins; D018836:Inflammation Mediators; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D016753:Interleukin-10; C044101:endotoxin, Escherichia coli