Erythropoietin (EPO) is being trialled in preterm infants to reduce
brain injury, but high doses increase
lung injury in ventilated preterm lambs. We aimed to determine whether early administration of lower doses of EPO could reduce ventilation-induced
lung injury and systemic
inflammation in preterm lambs. Ventilation was initiated in anaesthetized preterm lambs [125 ± 1 (SD) days gestation] using an injurious strategy for the first 15 min. Lambs were subsequently ventilated with a protective strategy for a total of 2 h. Lambs were randomized to receive either intravenous saline (Vent; n = 7) or intravenous 300 ( n = 5), 1,000 (EPO1000; n = 5), or 3,000 (EPO3000; n = 5) IU/kg of human recombinant EPO via an umbilical vein. Lung tissue was collected for molecular and histological assessment of
inflammation and injury and compared with unventilated control lambs (UVC; n = 8). All ventilated groups had similar blood gas and ventilation parameters, but EPO1000 lambs had a lower fraction of inspired
oxygen requirement and lower alveolar-arterial difference in
oxygen. Vent and EPO lambs had increased lung
interleukin (IL)-1β,
IL-6, and
IL-8 mRNA, early
lung injury genes
connective tissue growth factor,
early growth response protein 1, and
cysteine-rich 61, and liver serum
amyloid A3
mRNA compared with UVCs; no difference was observed between Vent and EPO groups. Histological
lung injury was increased in Vent and EPO groups compared with UVCs, but EPO3000 lambs had increased
lung injury scores compared with VENT only. Early low-doses of EPO do not exacerbate ventilation-induced
lung inflammation and injury and do not provide any short-term respiratory benefit. High doses (≥3,000 IU/kg) likely exacerbate
lung inflammation and injury in ventilated preterm lambs. NEW & NOTEWORTHY Trials are ongoing to assess the efficacy of
erythropoietin (EPO) to provide neuroprotection for preterm infants. However, high doses of EPO increase ventilation-induced
lung injury (VILI) in preterm lambs. We investigated whether early lower doses of EPO may reduce VILI. We found that lower doses did not reduce, but did not increase, VILI, while high doses (≥3,000 IU/kg) increase VILI. Therefore, lower doses of EPO should be used in preterm infants, particularly those receiving respiratory support.