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

Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, Canada

DW Paty

Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, Canada

SU Kim

Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, Canada

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

Key Words: human astrocyte • interferon- • interferon-β • interferon- • proliferation

Multiple Sclerosis, Vol. 1, No. 5, 279-287 (1996)
DOI: 10.1177/135245859600100504


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