Interferon-beta is a key regulator of proinflammatory events in experimental autoimmune encephalomyelitis

Interferon (IFN)-β is an effective therapy for relapsing-remitting multiple sclerosis, yet its mechanism of action remains ill-defined.

Our objective was to characterize the role of IFN-β in immune regulation in experimental autoimmune encephalomyelitis (EAE).

IFN-β(+/+) and IFN-β(-/-) mice were immunized with myelin oligodendrocyte glycoprotein peptide in the presence or absence of IFN-β, to induce EAE. Disease pathogenesis was monitored in the context of incidence, time of onset, clinical score, and immune cell activation in the brains, spleens and lymph nodes of affected mice.

Compared with IFN-β(+/+) mice, IFN-β(-/-) mice exhibited an earlier onset and a more rapid progression of EAE, increased numbers of CD11b(+) leukocytes infiltrating affected brains and an increased percentage of Th17 cells in the central nervous system and draining lymph nodes. IFN-β treatment delayed disease onset and reduced disease severity. Ex vivo experiments revealed that the lack of IFN-β results in enhanced generation of autoreactive T cells, a likely consequence of the absence of IFN-β-regulated events in both the CD4(+) T cells and antigen-presenting dendritic cells. Gene expression analysis of IFN-β-treated bone marrow macrophages (CD11b(+)) identified modulation of genes affecting T cell proliferation and Th17 differentiation.

We conclude that IFN-β acts to suppress the generation of autoimmune-inducing Th17 cells during the development of disease as well as modulating pro-inflammatory mediators.