Cytokine response during hyperoxia: sequential production of pulmonary tumor necrosis factor and interleukin-6 in neonatal rats.
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.
Ben-Ari
J
J
Division of Neonatology, Childrens Hospital Los Angeles, California, USA.
Makhoul
I R
IR
Dorio
R J
RJ
Buckley
S
S
Warburton
D
D
Walker
S M
SM
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*
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha