Neuroprotective role of IL-4 against activated microglia.

Abstract

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-gamma, we found that both LPS and TNF-alpha triggered neuronal cell injury (impairment of gamma-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-gamma priming of microglia with a subsequent decrease in the production of TNF-alpha and nitric oxide.