TY - JOUR
T1 - Erythropoietin augments the cytokine response to acute endotoxin-induced inflammation in humans
AU - Hojman, Pernille
AU - Taudorf, Sarah
AU - Lundby, Carsten
AU - Pedersen, Bente Klarlund
PY - 2009/3
Y1 - 2009/3
N2 - 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.
AB - 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.
KW - Adult
KW - Cytokines/immunology
KW - Endotoxins
KW - Erythropoietin/therapeutic use
KW - Humans
KW - Inflammation/chemically induced
KW - Inflammation Mediators
KW - Interleukin-10/blood
KW - Interleukin-6/blood
KW - Lymphocyte Count
KW - Male
KW - Neutrophils
KW - Recombinant Proteins
KW - Tumor Necrosis Factor-alpha/blood
U2 - 10.1016/j.cyto.2008.12.005
DO - 10.1016/j.cyto.2008.12.005
M3 - Journal article
C2 - 19167238
SN - 1043-4666
VL - 45
SP - 154
EP - 157
JO - Cytokine
JF - Cytokine
IS - 3
ER -