Counteracting effect of IFN-β on IFN-γ-induced proliferation of human astrocytes in culture

Abstract

Recent clinical trials have shown that interferon beta (IFN-β) is effective in reducing exacerbations in relapsing-remitting MS, while interferon gamma (IFN-γ) precipitates the relapses. To investigatge mechanisms underlying the beneficial effects of IFN-β and the detrimental effects of IFN-γ in MS, cell growth-regulatory effects of IFNs were examined in astrocyte-enriched cultures isolated from fetal brains of 12-20 weeks' gestation. Treatment with IFN-γ (50 or 500 IU ml-1) stimulated significantly the proliferation of astrocytes in 6 out of 9 culture series examined, while IFN-β (50 or 500 IU ml-1) inhibited the astrocytic proliferation in 3 out of 9 cultures, and IFN-α (50 or 500 IU ml-1) did not affect the proliferation. IFN-β and to a lesser degree IFN-α reduced the astrocytic proliferation induced by IFN-γ-treatment in 8 out of 9 culture series. The counteracting effect of IFN-α/IFN-β against IFN-γ-induced astrocytic proliferation was verified by the DNA content distribution analysis of propidium iodide-labeled cells. The antagonistic effect of IFN-α/IFN-β on the growth-promoting activity of IFN-γ in cultured human astrocytes suggests that interferons serve as growth regulators of astrocytes at sites of reactive gliosis lesions of MS. © 1996 Stockton Press All rights reserved.