IN-VIVO ANTIOXIDANT TREATMENT SUPPRESSES NUCLEAR FACTOR-KAPPA-B ACTIVATION AND NEUTROPHILIC LUNG INFLAMMATION

We hypothesized that endotoxin injection in rats would stimulate in vi vo nuclear factor-kappa B (NF-kappa B) activation in lung tissue and t hat antioxidant treatment before endotoxin injection would attenuate e ndotoxin-induced NF-kappa B activation, chemokine gene expression, and neutrophilic lung inflammation, We studied NF-kappa B activation in r at lung tissue following a single i.p. injection of endotoxin (6 mg/kg ), After in vivo endotoxin treatment, lung NF-kappa B activation peake d at 2 h and temporally correlated with the expression of cytokine-ind uced neutrophil chemoattractant mRNA in lung tissue, Treatment with th e;antioxidant N-acetylcysteine (NAG) 1 h before endotoxin resulted in decreased lung NF-kappa B activation in a dose-dependent manner (from 200-1000 mg/kg) and diminished cytokine-induced neutrophil chemoattrac tant mRNA expression in lung tissue, Treatment with NAC significantly suppressed endotoxin-induced neutrophilic alveolitis. The average tota l lung lavage neutrophil count was 5.5 x 10(6) with endotoxin treatmen t vs 0.9 x 10(6) with NAC treatment before endotoxin, The NF-kappa B p athway represents an attractive therapeutic target for strategies to c ontrol neutrophilic inflammation and lung injury.