Extreme prematurity-associated alterations of pulmonary inflammatory mediators before and after surfactant administration.

Abstract

The role of prematurity and pulmonary inflammation in the pathogenesis of bronchopulmonary dysplasia (BPD) is very well-defined. However, there is limited knowledge about whether the level of prematurity and surfactant therapy alter the pulmonary cytokines and endothelial growth factor (VEGF). This study analyzed the VEGF and cytokines, including interleukin (IL)-1β, IL-6, IL-8, and IL-10, and tumor necrosis factor α (TNF-α) in the tracheal aspirate (TA) of preterm infants obtained before (within 2h after birth) and 10-12h after the administration of the first dose of surfactant. TA was collected from 40 infants of 35 or fewer weeks of gestation, including extremely (Group 1, n=19), very (Group 2, n=13), and moderate/late (Group 2, n=8) preterm neonates. In addition to univariate analysis, controlled regression models estimated the association of perinatal factors with the tested parameters and their role in the development of BPD. We recorded significantly lower post-partum levels of VEGF and higher IL-8, IL-1β, and TNF-α in the TA of Group 1 infants than in Group 2 and 3. Compared to the infants in Group 2 and 3, the post-surfactant increases of pulmonary VEGF, IL-8, IL-10, and TNF-α were more significant in Group 1. All tested parameters in Group 1 and 2 infants, before and after surfactant administration, were comparable. BPD was recorded in nearly 60% of the extremely preterm survivors and was significantly predicted by increased IL-8 before, and elevated TNF-α level after surfactant administration. This study indicates the association of birth at extremely preterm gestation with reduction in pulmonary VEGF and exacerbation of pro-inflammatory cytokines followed by greater elevation post-surfactant administration levels of VEGF, IL-8, TNF-α, and IL-10 than in neonates born with gestational age of 28-35 weeks.