The Mechanism of Action of Interferon-β in Relapsing Multiple Sclerosis

@article{Kieseier2011TheMO,
  title={The Mechanism of Action of Interferon-$\beta$ in Relapsing Multiple Sclerosis},
  author={Bernd C. Kieseier},
  journal={CNS Drugs},
  year={2011},
  volume={25},
  pages={491-502}
}
  • B. Kieseier
  • Published 1 June 2011
  • Biology, Medicine
  • CNS Drugs
Multiple sclerosis (MS) is characterized by autoimmune inflammation and subsequent neurodegeneration. It is believed that early in the disease course, proinflammatory T cells that are activated in the periphery by antigen presentation cross the blood-brain barrier (BBB) into the CNS directed by various chemotaxic agents. However, to date, there has been no formal demonstration of a specific precipitating antigen. Once inside the CNS, activated T cells including T helper-1 (Th1), Th17, γδ and… 
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References

SHOWING 1-10 OF 110 REFERENCES
Immunomodulatory effects of interferon beta-1a in multiple sclerosis
T cells in multiple sclerosis and experimental autoimmune encephalomyelitis
TLDR
The contribution of Th1, Th17, γδ, CD8+ and regulatory T cells as well as the possible development of new therapeutic approaches for MS based on manipulating these T cell subtypes are reviewed.
Th17 Cells and autoimmune encephalomyelitis (EAE/MS).
  • T. Aranami, T. Yamamura
  • Biology, Medicine
    Allergology international : official journal of the Japanese Society of Allergology
  • 2008
TLDR
It is demonstrated that human Th17 cells could be identified as CCR2+ CCR5- memory CD4+ T cells, and accumulating evidences raise a possibility that C CR2 on Th17 Cells may be a therapeutic target in MS.
Pathogenesis of myelin/oligodendrocyte damage in multiple sclerosis
TLDR
This review describes recent and salient findings from animal models and human clinical studies that have established the current understanding of the distinct steps in the development of immune autoreactivity that culminates in the CNS lesions associated with MS.
An Interleukin (IL)-10/IL-12 Immunoregulatory Circuit Controls Susceptibility to Autoimmune Disease
TLDR
It is demonstrated that interleukin (IL)-12 is essential for the generation of the autoreactive Th1 cells that induce EAE, both in the presence and absence of interferon γ.
Regulatory T cells in the control of inflammatory demyelinating diseases of the central nervous system
TLDR
A better understanding of the induction of T regulatory cells, of their mechanisms of action, and of approaches to manipulate them in vivo may offer new therapeutic opportunities for patients with multiple sclerosis.
IL-1R Signaling within the Central Nervous System Regulates CXCL12 Expression at the Blood-Brain Barrier and Disease Severity during Experimental Autoimmune Encephalomyelitis1
TLDR
It is suggested that T cell-derived IL-1β contributes to loss of immune privilege during CNS autoimmunity via pathologic alteration in the expression of CXCL12 at the BBB.
Interferon beta induces T-helper 2 immune deviation in MS
TLDR
Interferon beta 1a (IFN-β) suppresses myelin basic protein (MBP)-reactive T cells and induces immune deviation toward the production of T-helper 2 cytokines, which may contribute to its therapeutic benefit in MS.
Interferon-β is neuroprotective against the toxicity induced by activated microglia
Interferon beta-1b decreases the migration of T lymphocytes in vitro: effects on matrix metalloproteinase-9.
TLDR
It is suggested that the clinical benefits of IFNbeta-1b treatment in MS patients may be in part a result of the ability of this drug to significantly decrease MMP-9 activity, leading to a reduction of T-lymphocyte infiltration into the CNS.
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