HYPEROXIA ACTIVATES NF-KAPPA-B AND INCREASES TNF-ALPHA AND IFN-GAMMA GENE-EXPRESSION IN MOUSE PULMONARY LYMPHOCYTES

Hyperoxia-associated production of reactive oxygen species leads to ne utrophil infiltration into the lungs and increased pulmonary proinflam matory cytokine expression. However, the initial events induced by hyp eroxia, and leading to acute inflammatory lung injury, remain incomple tely characterized. To explore this issue, we examined nuclear transcr iptional regulatory factor (NF-kappa B and NF-IL-6) activation and cyt okine expression in the lungs following 12 to 48 h of hyperoxia exposu re. No increases in cytokine (IL-1 beta, IL-6, IL-10 TGF-beta, TNF-alp ha, IFN-gamma) expression nor in NF-kappa B activation were found afte r 12 h of hyperoxia. Following 24 h of hyperoxia, NF-kappa B activatio n and increased levels of TNF-alpha mRNA were present in pulmonary lym phocytes. By 48 h of hyperoxia, amounts of IFN-gamma and TNF-alpha pro tein as well as mRNA were increased in the lungs, and NF-kappa B conti nued to show activation, even though no histologic abnormalities were present. These results show that hyperoxia activates NF-kappa B in the lungs before any increase in proinflammatory cytokine protein occurs, and suggest that NF-kappa B activation may represent an initial event in the proinflammatory sequence induced by hyperoxia.