Immune and non-immune actions of interferon-beta-Ib on primary human neural cells.
Systemic interferon-beta-Ib (IFN-beta-Ib) reduces the frequency of clinical exacerbations and the number of magnetic resonance imaging (MRI)-defined lesions in patients with relapsing-remitting MS. The basis for this clinical effect is not understood. While IFN-beta-Ib has been demonstrated to have antiproliferative and immunomodulatory effects on the systemic immune system, its actions on neural cells could also contribute to its therapeutic efficacy. In this study, we have examined possible immune and non-immune effects of IFN-beta-Ib on CNS-derived primary human cells. With respect to immune-related effects, application of IFN-beta-Ib did not decrease basal expression of HLA-DR on astrocytes or microglia, and it reduced the IFN-gamma-enhanced HLA-DR expression on adult human astrocytes only at high concentrations (1000 IU ml-1); IFN-beta-Ib at all concentrations tested did not reduce the IFN-gamma-enhanced HLA-DR expression by fetal astrocytes or adult microglial cells. In contrast, but in correspondence with the literature, the IFN-gamma-enhanced HLA-DR expression on a glioma cell line was attenuated by IFN-beta-Ib in a dose-dependent manner. With respect to non-immune effects, the number of adult human oligodendrocytes and their state of morphological differentiation were not affected by IFN-beta-Ib. Proliferation of the mitotically active fetal human astrocytes, however, was reduced by IFN-beta-Ib treatment. Lactate dehydrogenase assays revealed that IFN-beta-Ib was not toxic to neural cells, including adult oligodendrocytes and fetal human neurons. We conclude that IFN-beta-Ib lacks efficacy in down-regulating HLA-DR expression by primary human neural cells and that regulation of MHC class II antigens is unlikely to be a mechanism for its beneficial effect in MS. Finally, the lack of toxicity of IFN-beta-Ib on human neural cells is important for a drug that will probably be used widely.
McLaurin
J
J
Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Quebec, Canada.
Antel
J P
JP
Yong
V W
VW
D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000276:immunology* / Q000494:pharmacology*; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*
D006684:HLA-DR Antigens; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a