Differential NF-κB activation after intratracheal endotoxin

We examined the relationship between nuclear factor (NF)-kappa B DNA binding activity, cytokine gene expression, and neutrophilic alveolitis in rats after intratracheal (IT) instillation of endotoxin [lipopolysaccharide (LPS)]. NF-kappa B activation in lung tissue mirrored neutrophilic alveolitis after IT LPS instillation, with NF-kappa B activation and neutrophilic influx beginning 2 h after IT LPS doses of 0.01 mg/kg or greater. In lung lavage fluid cells, however, transient NF-kappa B activation was present in alveolar macrophages by 15 min after IT LPS instillation, followed by a second peak of NF-kappa B activation corresponding to the onset on neutrophilic alveolitis. For cytokines thought to be NF-kappa B dependent, two different patterns of mRNA expression were found. Interleukin (IL)-1 alpha, IL-1 beta, and tumor necrosis factor-or showed increased mRNA by 30 min after IT LPS instillation, but IL-6- and cytokine-induced neutrophil chemoattractant mRNAs were not substantially increased until 2 h after IT LPS instillation. Therefore, IT LPS causes differential NF-kappa B activation in air space cells and lung tissue, which likely determines production of key cytokines and directs the evolution of neutrophilic alveolitis.