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 clemyelination, T lymphocyte infiltration, and neuronal degeneration. lnterferon-beta (IFN)-beta reduces symptoms of the relapsing-remitting form of MS. In this study, we investigated whether IFN-beta is neuroprotective against the toxicity induced by activated microglia in cortical neurons and microglia co-cultures. IFN-beta suppressed the production of glutamate and superoxide by activated microglia. to 70% and 75% of lipopolysaccharide stimulation, respectively, and prevented microglial-incluced neuronal cell death. Although IFN-beta enhanced the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and nitric oxide (NO) by activated microglia, these molecules did not directly induce neurotoxicity in cultured cortical neurons. IFN-beta 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 alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). These results suggest that IFN-beta may be a useful agent counteracting neurotoxicity associated with activated microglia. (c) 2007 Elsevier B.V. All rights reserved.