Journal Article

Inflammatory Mediators in Tracheal Aspirates of Preterm Infants Participating in a Randomized Trial of Inhaled Nitric Oxide

Zemlin, Michael, Maier, Rolf F., Fuchs, Hans W., Uhlig, Stefan, Hummler, Helmut D., Thome, Ulrich H., Mercier, Jean-Christophe, Amann, Elena, Uhlig, Ulrike, Yang, Yang, Laube, Mandy

2017

Overview

Ventilated preterm infants frequently develop bronchopulmonary dysplasia (BPD) which is associated with elevated inflammatory mediators in their tracheal aspirates (TA). In animal models of BPD, inhaled nitric oxide (iNO) has been shown to reduce lung inflammation, but data for human preterm infants is missing. Within a European multicenter trial of NO inhalation for preterm infants to prevent BPD (EUNO), TA was collected to determine the effects of iNO on pulmonary inflammation. TA was collected from 43 premature infants randomly assigned to receive either iNO or placebo gas (birth weight 530-1230 g, median 800 g, gestational age 24 to 28 2/7 weeks, median 26 weeks). Interleukin (IL)-1β, IL-6, IL-8, transforming growth factor (TGF)-β1, interferon γ-induced protein 10 (IP-10), macrophage inflammatory protein (MIP)-1α, acid sphingomyelinase (ASM), neuropeptide Y and leukotriene B4 were measured in serial TA samples from postnatal day 2 to 14. Furthermore, TA levels of nitrotyrosine and nitrite were determined under iNO therapy. The TA levels of IP-10, IL-6, IL-8, MIP-1α, IL-1β, ASM and albumin increased with advancing postnatal age in critically ill preterm infants, whereas nitrotyrosine TA levels declined in both, iNO-treated and placebo-treated infants. The iNO treatment generally increased nitrite TA levels, whereas nitrotyrosine TA levels were not affected by iNO treatment. Furthermore, iNO treatment transiently reduced early inflammatory and fibrotic markers associated with BPD development including TGF-β1, IP-10 and IL-8, but induced a delayed increase of ASM TA levels. Treatment with iNO may have played a role in reducing several inflammatory and fibrotic mediators in TA of preterm infants compared to placebo-treated infants. However, survival without BPD was not affected in the main EUNO trial. NCT00551642.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Administration, Inhalation / Albumins - metabolism / Analysis / Analysis of Variance / Animal models / Apoptosis / Biology and Life Sciences / Birth weight / Bronchopulmonary dysplasia / Care and treatment / Case-Control Studies / Chemokines - metabolism / Critical care / Cytokines / Demography / Dysplasia / Enrollments / Female / Fibrosis / Free radicals / Gene expression / Gestational age / Growth factors / Health aspects / Humans / Infant, Newborn / Infant, Premature - metabolism / Infants / Inflammation / Inflammation mediators / Inflammation Mediators - metabolism / Inhalation / Interferon / Interleukin / Interleukin 6 / Interleukin 8 / IP-10 protein / Leukotriene B4 / Lung diseases / Macrophage inflammatory protein / Macrophages / Male / Medicine and Health Sciences / Neuropeptide Y / Newborn babies / Nitric oxide / Nitric Oxide - administration & dosage / Nitrites - metabolism / Nitrotyrosine / Pediatrics / People and Places / Pharmacology / Physical Sciences / Premature babies / Premature infants / Research and Analysis Methods / Respiration / Respiratory distress syndrome / Respiratory therapy / Rodents / Sphingomyelin phosphodiesterase / Sphingomyelin Phosphodiesterase - metabolism / Suction / Surfactants / Toxicology / Trachea / Trachea - metabolism / Transforming growth factor / Transforming growth factor-b1 / Tyrosine - analogs & derivatives / Tyrosine - metabolism / Ventilation / Ventilators