Hyperoxia-derived lung damage in preterm infants

Abstract

Hyperoxia-induced lung injury is characterized by an influx of inflammatory cells, increased pulmonary permeability, endothelial and epithelial cell death. This review highlights the mechanistic aspects of inflammation, vascular leak and cell death. The focus will be on agents that contribute to hyperoxia-induced lung injury in developmentally appropriate animal models, and those that have been detected in human premature neonates.

Figure 1

Photomicrographs (×110, upper panel; ×20 lower panel; hematoxylin and eosin stain) of neonatal lung injury noted in newborn mice at postnatal day 2, after 100% O₂ exposure since birth. Note the alveolar exudates and presence of inflammatory cells in the hyperoxia-exposed lungs, compared with litter-mate controls in room air. RA, room air; HYP, hyperoxia.

Figure 2

A proposed model of hyperoxia-derived lung damage in neonates delineating some of the pathways. Hyperoxia exposure leads to release of certain mediators [exemplified by vascular endothelial growth factor (VEGF) and angiopoietin 2] that disrupt the alveolar–capillary membrane leading to pulmonary edema which contributes to lung injury. Other cytokines [examples of which are interleukin (IL)-1, IL-6, IL-8, transforming growth factor (TGF) β, tumor necrosis factor (TNF) α, VEGF] are also released from lung cells that attract inflammatory cells to the lung. These inflammatory cells as well as hyperoxia per se release reactive oxygen species, which can initiate the mitochondrial-dependent cell death pathway. The cytokines and cell death mediators contribute to pulmonary injury resulting in hyperoxia-derived lung damage. PKC, protein kinase C.