Interferon gamma (IFN-gamma) has been shown to be produced within multiple
sclerosis (MS) lesions by infiltrating lymphocytes: systemic administration
of this cytokine induces exacerbation of the disease. The aim of the curre
nt study was to establish the contribution of IFN-gamma to oligodendrocyte
(OL) injury. Our studies utilized cultured human OLs, obtained by dissociat
ion of surgically derived non-MS adult brain tissue. Neither cell survival
nor myelin basic protein (MBP) gene expression were affected after 96 hours
of treatment with IFN-gamma (100 U/ml), as assessed by LDH release, nucleo
some enrichment assay, and RT-PCR. Expression of the death receptor Fas (CD
95, APO-1) was, however, significantly increased. Furthermore, IFN-gamma-tr
eated OLs became susceptible to Fas-mediated apoptosis when compared with u
ntreated cells, and were protected by pretreatment with the caspase inhibit
or ZVAD. TNF-alpha augmented the IFN-gamma-induced effect. Our results thus
indicate that IFN-gamma is not directly cytotoxic for human OLs in culture
, but could indirectly modulate functional injury-related responses by upre
gulating Fas on the cell surface.