Microglia have been proposed to play a pathogenetic role in immunologically mediated neurodegenerative diseases. In our study, using microglial/neuronal cell cocultures primed with IFN-γ, we found that both LPS and TNF-α triggered neuronal cell injury (impairment of γ-aminobutyric acid uptake and neuronal loss) via a nitric oxide mechanism. Pretreatment of cell cocultures with IL-4, an immunosuppressive cytokine, prevented, in a dose-dependent manner, neuronal cell injury induced by activated microglia. The mechanism by which IL-4 exerts its neuroprotective effect was found to involve the inhibition of IFN-γ priming of microglia with a subsequent decrease in the production of TNF-α and nitric oxide.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of Immunology|
|State||Published - 1993|