title: Inflammatory Mediators in Tracheal Aspirates of Preterm Infants Participating in a Randomized Trial of Inhaled Nitric Oxide.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  NCT00551642.
authors.affiliation: Center for Pediatric Research Leipzig, Hospital for Children & Adolescents, Division of Neonatology, University of Leipzig, Leipzig, Germany.
authors.forename: Mandy
authors.identifier: http://orcid.org/0000-0002-7180-2858
authors.initials: M
authors.lastname: Laube
authors.affiliation: Division of Neonatology and Pediatric Critical Care, Department of Pediatrics, University of Ulm, Ulm, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Amann
authors.affiliation: Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Uhlig
authors.affiliation: Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Hans W
authors.initials: HW
authors.lastname: Fuchs
authors.affiliation: Department of Pediatrics, University of Marburg, Marburg, Germany.|Department of Pediatrics, University of Saarland, Homburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Zemlin
authors.affiliation: Hôpital Universitaire Robert Debré, Paris, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Mercier
authors.affiliation: Department of Pediatrics, University of Marburg, Marburg, Germany.
authors.forename: Rolf F
authors.initials: RF
authors.lastname: Maier
authors.affiliation: Division of Neonatology and Pediatric Critical Care, Department of Pediatrics, University of Ulm, Ulm, Germany.
authors.forename: Helmut D
authors.initials: HD
authors.lastname: Hummler
authors.affiliation: Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Uhlig
authors.affiliation: Center for Pediatric Research Leipzig, Hospital for Children & Adolescents, Division of Neonatology, University of Leipzig, Leipzig, Germany.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Thome
mesh_terms: D000280:Administration, Inhalation; D000418:Albumins / Q000378:metabolism; D000704:Analysis of Variance; D016022:Case-Control Studies; D018925:Chemokines / Q000378:metabolism; D003710:Demography; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage*; D009573:Nitrites / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013396:Suction; D014132:Trachea / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000418:Albumins; D018925:Chemokines; D018836:Inflammation Mediators; D009573:Nitrites; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D013108:Sphingomyelin Phosphodiesterase