Silica-induced pulmonary inflammation in rats: Activation of NF-kappa B and its suppression by dexamethasone

The goal of this study was to examine the relationship of the transcription al regulatory factor nuclear factor-kappaB (NF-kappa B) to the early inflam matory events involved with silica exposure. Male F-344 rats received an in tratracheal (i.t.) instillation of silica (100 mg/kg in a volume of 1 ml/kg ) of saline. At 1, 3, 6, and 18 h postinstillation, and the rats were sacri ficed and underwent bronchoalveolar lavage (BAL) for functional analysis of inflammation. Beginning at I h postinstillation, the silica-instilled (Si) rats displayed significant increases in neutrophils in BAL fluid compared to the saline controls. BAL cells from the Si group displayed a significant increase in luminol-dependent chemiluminescence (LDCL) compared to the con trols. NF-KB activation was measurable at 3 h postinstillation, and this ac tivation continued throughout the 18-h time course. Treatment with dexameth asone (5 mg/kg) at -3 h prior to silica instillation, at the time of instil lation (0 h), and +1.5 h postinstillation resulted in both a reduction in N F-KB expression (by 70%) at 3 h postinstillation and corresponding reductio ns in LDCL, BAL cell count, and BAL neutrophils. These results show that ac tivation of NF-KB is associated with silica-induced pulmonary inflammation, and the inhibition of its activation correlates temporally with suppressio n of inflammation (C) 1998 Academic Press.