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% O-2 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% O-2 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% O-2 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 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 the known inflammatory and anti-inflammatory role of these cytokines.