Cytokine response during hyperoxia: sequential production of pulmonary tumor necrosis factor and interleukin-6 in neonatal rats

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. To determine the involvement of tumor...

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Bibliographic Details
Published in:The Israel Medical Association journal 2000-05, Vol.2 (5), p.365-369
Main Authors: Ben-Ari, J, Makhoul, I R, Dorio, R J, Buckley, S, Warburton, D, Walker, S M
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Bronchoalveolar Lavage Fluid - immunology
Bronchopulmonary Dysplasia - immunology
Bronchopulmonary Dysplasia - pathology
Cytokines - metabolism
Disease Models, Animal
Female
Humans
Hyperoxia - immunology
Hyperoxia - pathology
Infant, Newborn
Interleukin-6 - metabolism
Lung - immunology
Lung - pathology
Male
Oxygen Inhalation Therapy
Rats
Rats, Sprague-Dawley
Tumor Necrosis Factor-alpha - metabolism
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Summary: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. To determine the involvement of tumor necrosis factor-alpha and interleukin-6 in lung injury in neonatal rats exposed to 100% O2 concentration. 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. 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). 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.
ISSN:1565-1088