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Cytokine. 2014 Sep;69(1):22-8. doi: 10.1016/j.cyto.2014.04.009. Epub 2014 Jun 2.

Endogenous erythropoietin varies significantly with inflammation-related proteins in extremely premature newborns.

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Nationwide Children's Hospital, and The Ohio State University, Columbus, OH, USA. Electronic address:
Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Boston, MA, USA; Harvard School of Public Health, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA; Department of Obstetrics, Gynecology and Reproductive Biology, Boston, MA, USA; Brigham and Women's Hospital, Boston, MA, USA.
East Carolina University School of Medicine, Greenville, NC, USA.
Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA; Perinatal Neuroepidemiology Unit, Hannover Medical School, Hannover, Germany.
Harvard Medical School, Boston, MA, USA; Boston Children's Hospital, Boston, MA, USA.



Erythropoietin, a pluripotent glycoprotein essential for erythropoiesis, fetal growth, and development, has recently been implicated in innate immune regulation. Data from the ELGAN Study allowed us to evaluate relationships between endogenous erythropoietin and 25 inflammation-related proteins in extremely premature newborns.


We measured the concentrations of 25 inflammation-related proteins and of erythropoietin in blood spots collected on postnatal days 1, 7, and 14 from 936 infants born before 28 weeks gestation. We calculated the odds that infants with an inflammation-related protein in the highest quartile for gestational age and collection day had an erythropoietin concentration in the highest or lowest quartile.


The proportion of children with inflammation-associated protein concentrations in the top quartile tended to increase monotonically with increasing quartile of EPO concentrations on 2 of the 3 days assessed. To a large extent, on each of the 3 days assessed, the odds ratios for an erythropoietin concentration in the top quartile were significantly elevated among those with an inflammation-related protein concentration in the top quartile.


Our findings suggest that in very preterm newborns, circulating levels of endogenous erythropoietin vary significantly with circulating levels of inflammation-related proteins. Elevation of endogenous erythropoietin might not be an epiphenomenon, but instead might contribute to subsequent events, by either promoting or reducing inflammation, or by promoting an anti-injury or repair capability.


Acute-phase; Cytokine; Infant; Premature; Protein

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