Discordant pulmonary proinflammatory cytokine expression during acute hyperoxia in the newborn rabbit

Newborn animals are resistant to oxygen toxicity. lo investigate this pheno menon, the proinflammatory cytokines interleukin (IL)-1 beta, IL-8, and mon ocyte chemoattractant protein-1 (MCP-1) were measured during newborn rabbit hyperoxic lung injury. Pups were exposed to >95% O-2 for 8-9 days, followe d by 60% O-2 until 36 days of age. Lung lavage fluid, RNA, and tissue secti ons were collected at 0, 2, 4, 6, 8, 10, 12, 14, 22, and 36 days. Acute inf lammation occurred by 6-10 days of hyperoxia, and fibrosis by 22 days. Nort hern hybridization a lung homogenates from hyperoxia-exposed pups showed el evated MCP-1 and IL-8 mRNA expression at 6 and 10 days, respectively, compa red to age-matched, air-exposed controls. Lavage fluid IL-8 protein also pe aked at 10 days, and was strongly correlated to neutrophil numbers in lavag e. In situ hybridization revealed elevated IL-1 beta mRNA in macrophages, a lveolar epithelial and interstitial cells at 2-10 days, elevated MCP-1 mRNA in similar cell types at 4-8 days, and elevated IL-8 mRNA in these cells a nd neutrophils at 4-10 days. IL-1 beta and IL-8 expression peaked during pe ak inflammation, whereas peak MCP-1 expression preceded macrophage influx. Comparing newborn and adult animals' chemokine responses may help explain t heir differences in hyperoxia susceptibility.