Accumulating evidence indicates that interferon-beta (IFN-beta) can modify the complex immunopathogenic scenario causing clinical relapse activity and disease progression in MS. However, the beneficial effects of IFN-beta in MS patients may also depend on non-immune mechanisms, including the modulation of astrocyte function. In the present report, we have shown that, depending on the dose, IFN-beta treatment can either promote astrocyte proliferation and survival, or result astrocyte death. These actions depend, at least in part, on the regulation of nuclear factor-kappa B (NF-kappa B), an inducible transcription factor present in neurons and glia. This bimodal effect of IFN-beta adds a new layer of complexity in the actions of IFN-beta within the CNS. (C) 2010 Elsevier B.V. All rights reserved.