J. Ben-ari et al., Cytokine response during hyperoxia: Sequential production of pulmonary tumor necrosis factor and interleukin-6 in neonatal rats, ISR MED ASS, 2(5), 2000, pp. 365-369
Background: Exposure of newborn animals to high concentrations of oxygen le
ads to diffuse alveolar damage similar to that seen in bronchopulmonary dys
plasia 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% O-2 concentra
tion.
Methods: A randomized controlled study was designed in which litters of ter
m Sprague-Dawley rat pups were assigned to experimental or control groups.
The pups in the experimental group were placed in 100% O-2 from birth for 9
days, while the control pups were placed in room air. Twelve to 15 pups fr
om each group were sacrificed on day 1, 3, 6, 9 and 13 after birth for bron
choalveolar lavage collection and lung histologic study. The bronchoalveola
r lavage fluid was assayed for TNF alpha and IL-6.
Results: Newborn rats exposed to 100% O-2 for the first 9 days of life show
ed severe pulmonary edema and hypercellularity on days 1 and 3, which then
improved to nearly complete resolution on days 6 and 9. Pulmonary TNFa was
produced early on O-2 exposure (day 3) and pulmonary IL-6 later (days 6 and
9).
Conclusions: Hyperoxia induces sequential production of pulmonary TNFa and
IL-6, which corresponds to the severity of the pathological findings and th
e known inflammatory and anti-inflammatory role of these cytokines.