Interferon-β is neuroprotective against the toxicity induced by activated microglia

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system characterized by demyelination, T lymphocyte infiltration, and neuronal degeneration. Interferon-β (IFN)-β reduces symptoms of the relapsing–remitting form of MS. In this study, we investigated whether IFN-β is neuroprotective against the toxicity induced by activated microglia in cortical neurons and microglia co-cultures. IFN-β suppressed the production of glutamate and superoxide by activated microglia to 70% and 75% of lipopolysaccharide stimulation, respectively, and prevented microglial-induced neuronal cell death. Although IFN-β enhanced the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and nitric oxide (NO) by activated microglia, these molecules did not directly induce neurotoxicity in cultured cortical neurons. IFN-β did not prevent neuronal cell death induced by the peroxynitrite donor 3-morpholinosydnonimine (SIN-1) or ionotropic glutamate receptor agonists such as N-methyl-d-aspartic acid (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). These results suggest that IFN-β may be a useful agent counteracting neurotoxicity associated with activated microglia.