Cytotoxicity in cytokine stimulated astrocyte cultures: role of IL‐6 and nitric oxide

Abstract

SUMMARY The cytokines interleukin 1 (IL-l) and tumor necrosis factor alpha (TNF-a), produced by glial cells within the brain, appear to contribute to the neuropathogenesis of several inflammatory neurodegenerative diseases. However, little is known about the mechanism underlying cytokineinduced neurotoxicity. Using astroglial cultures obtained from fetal rat brain, we investigated the effects of lipopolysaccharides (LPS) and cytokines (IL- 1 p and TNF-a). Primary cell cultures treated with LPS, IL-l p plus TNF-a generated substantial amounts of nitric oxide (NO), elevated interleukin 6 (IL-6) levels and caused astroglial injury measured by lactate dehydrogenase (LDH) activity. However, blockade of NO production with nitric oxide synthase (NOS) inhibitors did not affect cell death, suggesting that NO is not responsible for cytokine-induced astroglial cell death under the experimental conditions employed.