Counteracting effect of IFN-beta on IFN-gamma-induced proliferation of human astrocytes in culture.

Abstract

Recent clinical trials have shown that interferon beta (IFN-beta) is effective in reducing exacerbations in relapsing-remitting MS, while interferon gamma (IFN-gamma) precipitates the relapses. To investigate mechanisms underlying the beneficial effects of IFN-beta and the detrimental effects of IFN-gamma 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-gamma (50 or 500 IU ml-1) stimulated significantly the proliferation of astrocytes in 6 out of 9 culture series examined, while IFN-beta (50 or 500 IU ml-1) inhibited the astrocytic proliferation in 3 out of 9 cultures, and IFN-alpha (50 or 500 IU ml-1) did not affect the proliferation IFN-beta and to a lesser degree IFN-alpha reduced the astrocytic proliferation induced by IFN-gamma-treatment in 8 out of 9 culture series. The counteracting effect of IFN-alpha/IFN-beta against IFN-gamma-induced astrocytic proliferation was verified by the DNA content distribution analysis of propidium iodide-labeled cells. The antagonistic effect of IFN-alpha/IFN-beta on the growth-promoting activity of IFN-gamma in cultured human astrocytes suggests that interferons serve as growth regulators of astrocytes at sites of reactive gliosis lesions of MS.