title: Cytokine response during hyperoxia: sequential production of pulmonary tumor necrosis factor and interleukin-6 in neonatal rats.
abstract: BACKGROUND
  Exposure of newborn animals to high concentrations of oxygen leads to diffuse alveolar damage similar to that seen in bronchopulmonary dysplasia in human infants. Therefore, neonatal rats are a suitable practical model of hyperoxic lung damage in human infants.
  
  
  OBJECTIVE
  To determine the involvement of tumor necrosis factor-alpha and interleukin-6 in lung injury in neonatal rats exposed to 100% O2 concentration.
  
  
  METHODS
  A randomized controlled study was designed in which litters of term Sprague-Dawley rat pups were assigned to experimental or control groups. The pups in the experimental group were placed in 100% O2 from birth for 9 days, while the control pups were placed in room air. Twelve to 15 pups from each group were sacrificed on day 1, 3, 6, 9 and 13 after birth for bronchoalveolar lavage collection and lung histologic study. The bronchoalveolar lavage fluid was assayed for TNF alpha and IL-6.
  
  
  RESULTS
  Newborn rats exposed to 100% O2 for the first 9 days of life showed severe pulmonary edema and hypercellularity on days 1 and 3, which then improved to nearly complete resolution on days 6 and 9. Pulmonary TNF alpha was produced early on O2 exposure (day 3) and pulmonary IL-6 later (days 6 and 9).
  
  
  CONCLUSIONS
  Hyperoxia induces sequential production of pulmonary TNF alpha and IL-6, which corresponds to the severity of the pathological findings and the known inflammatory and anti-inflammatory role of these cytokines.
authors.affiliation: Division of Neonatology, Childrens Hospital Los Angeles, California, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ben-Ari
authors.forename: I R
authors.initials: IR
authors.lastname: Makhoul
authors.forename: R J
authors.initials: RJ
authors.lastname: Dorio
authors.forename: S
authors.initials: S
authors.lastname: Buckley
authors.forename: D
authors.initials: D
authors.lastname: Warburton
authors.forename: S M
authors.initials: SM
authors.lastname: Walker
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D001997:Bronchopulmonary Dysplasia / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018496:Hyperoxia / Q000276:immunology* / Q000473:pathology; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008297:Male; D010102:Oxygen Inhalation Therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha