Friday, 4 December 2015

How does beta interferon really work?

Tao Y, Zhang X, Zivadinov R, Dwyer MG, Kennedy C, Bergsland N, Ramasamy D, Durfee J, Hojnacki D, Hayward B, Dangond F, Weinstock-Guttman B, Markovic-Plese S.Immunologic and MRI markers of the therapeutic effect of IFN-β-1a in relapsing-remitting MS. Neurol Neuroimmunol Neuroinflamm. 2015;2(6):e176.


OBJECTIVES:To assess potential roles of effector cells and immunologic markers in demyelinating CNS lesion formation, and their modulation by interferon β-1a (IFN-β-1a).
METHODS:Twenty-three patients with relapsing-remitting multiple sclerosis (RRMS) received IFN-β-1a for 6 months. Immunologic marker results were correlated with brain MRI lesion volumes, and volumes of normal-appearing brain tissue (NABT) with decreasing or increasing voxel-wise magnetization transfer ratio (VW-MTR), suggestive of demyelination and remyelination, respectively.
RESULTS:Baseline expression of Th22 cell transcription factor aryl hydrocarbon receptor (AHR) and interleukin (IL)-17F, and percentages of IL-22-expressing CD4+ and CD8+ cells, were significantly higher in patients vs 15 healthy controls; IL-4 in CD4+ cells was lower. Baseline percentage of IL-22-producing CD8+ cells positively correlated with T2 lesion volumes, while percentage of IL-17A-producing CD8+ cells positively correlated with T2 and T1 lesion volumes. IFN-β-1a induced reductions in transcription factor AHR, T-bet, and retinoic acid-related orphan nuclear hormone receptor C (RORc) gene expression, while it increased GATA3's expression in CD4+ cells. Percentages of IL-22-, IL-17A-, and IL-17F-expressing T cells significantly decreased following treatment. Increased percentages of IL-10-expressing CD4+ and CD8+ cells correlated with greater NABT volume with increasing VW-MTR, while decreased percentage of IL-17F-expressing CD4+ cells positively correlated with decreased NABT volume with decreasing VW-MTR.
CONCLUSIONS:Findings indicate that IFN-β-1a suppresses Th22 and Th17 cell responses, which were associated with decreased MRI-detectable demyelination.
How does copaxone work is a something that changes every few months, but how do interferons really work is another mistery, in this study they implicate a block of cytokines that T cell subsets. However is this direct or indirect and downstream of the real effect.  interferons block viral replication and by the same mechanism they block immune cell proliferation also and maybe this is at the centre of activity. 

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