The introduction of surfactant therapy for hyaline membrane disease, or respiratory distress syndrome of the newborn (RDS), has been associated with important reductions in mortality and in the duration of assisted ventilation required for most infants (1). For most premature infants, RDS is an acute disease that resolves with minimal long-term sequelae. However, a substantial minority of preterm infants, especially among those born at less than 28 wk of gestation, requires a prolonged period of assisted ventilation or oxygen supplementation, and develop bronchopulmonary dysplasia (BPD). A considerable body of evidence supports the notion that inflammation plays an important role in the pathophysiology of BPD (2,3). A lung inflammatory response leading to BPD can be initiated and promoted by both antenatal and postnatal factors. The most important known trigger of antenatal inflammation is chorioamnionitis, which can be either overt or subclinical. Postnatal factors that promote pulmonary inflammation include exposure to high levels of inspired oxygen, baro and stretch trauma, and infections. How do these inflammatory triggers influence the course of RDS and the development of BPD, and by what mechanism(s) do they mediate their effects? The study of Cheah et al. (4) in this issue addresses a mechanism thought to play a central role in many aspects of the inflammatory response.

In their study, Cheah et al. examine the activation of NF-κB in inflammatory cells in tracheal aspirates of infants with RDS, and evaluate correlations of NF-κB activation status with risk factors and clinical outcome. NF-κB is a logical choice for investigation, as it is at the center of the signal transduction networks governing the expression of cytokines and chemokines including TNF-alpha, IL-1β, IL-8, and many other inflammatory mediators (5). Cheah et al. assessed NF-κB activation using immunofluorescent staining to detect nuclear localization of this molecule. In the unstimulated cell, NF-κB is primarily localized in the cytoplasm, in a complex with its inhibitor IκB. Activation of inflammatory signaling pathways results in the degradation of IκB, which allows NF-κB to move into the nucleus, where it binds to specific promoter sites and stimulates transcription of inflammatory genes. NF-κB activation can be triggered by multiple processes associated with lung injury, including infections, hyperoxia, barotrauma and ventilatory stretch. Cheah et al. found that infants with evidence of nuclear localization of NF-κB activation in leukocytes in at least one tracheal aspirate sample required a longer duration of mechanical ventilation than infants in whom all samples were negative, and had higher levels of TNF-α in the tracheal aspirate fluid. NF-κB activation was strongly correlated with a history of chorioamnionitis. However, IL-8 concentrations were not increased, the numbers and proportions of neutrophils and monocytes did not differ in “positive” and “negative” infants, and NF-κB activation status had no predictive value for the subsequent development of BPD.

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