Effects of interferon-beta on microglial functions as inflammatory and antigen presenting cells in the central nervous system.
Interferon-beta (IFNbeta) reduces exacerbations of the relapsing-remitting form of multiple sclerosis (MS), but the exact mechanisms by which it exerts its beneficial effects are unknown. In this study, we examined the effects of IFNbeta on microglial functions, as either antigen presenting cells or effector cells for inflammatory demyelination. IFNbeta significantly suppressed the expression of class II MHC antigen and the co-stimulatory molecule B7-1 in microglia. It also suppressed microglial IL-12 production and differentiation of myelin oligodendrocyte glycoprotein (MOG)-sensitized T cells into the T helper 1 phenotype, which use microglia as antigen presenting cells. However, IFNbeta significantly and dose-dependently enhanced the production of inflammatory mediators for demyelination, such as TNFalpha, IL-1beta, IL-6, and nitric oxide (NO). The upregulation of inflammatory mediators was effectively suppressed with a phosphodiesterase inhibitor. Thus, IFNbeta may exert its suppressive effects in the induction phase, but not in the effector phase of MS. Side effects of IFNbeta treatment may be due to elevation of pro-inflammatory cytokines, and may be reduced by co-treatment with phosphodiesterase inhibitors.
Kawanokuchi
Jun
J
Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Mizuno
Tetsuya
T
Kato
Hideki
H
Mitsuma
Norimasa
N
Suzumura
Akio
A
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016899:Interferon-beta / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology* / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta