Erythropoietin inhibits cytokine production of neonatal and adult leukocytes.
BACKGROUND
Erythropoietin (Epo) was originally defined as a hematopoietic growth factor, but also has potent tissue-protective properties. The cytokine-modulating actions of Epo have received scant attention. We hypothesized that Epo significantly influences the in vitro cytokine production in both neonates and adults.


METHODS
The effects of Epo were investigated using a standardized in vitro whole blood assay. Production of various cytokines was assessed by means of intracellular cytokine detection (IL-2, -6, -8, IFN-gamma and TNF-alpha) in preterm infants, term neonates and adults. Furthermore, synthesis of IL-4, -5 and -10 in adults was investigated via cytometric bead array.


RESULTS
Epo significantly inhibits the production of various cytokines in preterm infants, term neonates and adults. In CD3+ lymphocytes, Epo predominantly decreases the number of IL-2-positive cells in all age groups. Similarly, in CD14+ cells, Epo significantly diminishes the number of IL-6- and TNF-alpha-producing cells. Furthermore, Epo significantly inhibits the synthesis of IL-4, IL-5 and IL-10 in adults.


CONCLUSIONS
rhEpo has significant inhibitory potential on the production of various cytokines by leukocytes in preterm and term infants as well as in adults. The described effect likely contributes to the tissue protective properties of Epo.
Strunk
Tobias
T
Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany. tobiasstrunk@yahoo.de
Härtel
Christoph
C
Temming
Petra
P
Matzke
Nadja
N
Zimmer
Janna
J
Schultz
Christian
C
D000328:Adult; D018929:Cell Culture Techniques; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007378:Interleukins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D007371:Interferon-gamma