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Multiple sclerosis (MS) is a complex genetic,
autoimmune disease associated with harmful inflammation in the central
nerve system (CNS). The clinical symptoms often appear during young
adulthood. If untreated, about 50% of all MS patients need walking aids
within ten years after clinical onset. Over the last two decades, a
protein modulating response of the immune system called interferon beta (IFNβ;
drug names: Betaseron, Avonex, Rebif) has been approved and is being used
as the first choice of treatment for MS. IFNβ treatment significantly
reduces the burden of disease in patients with MS. However, after several
courses of treatment, IFNβ can lead to detrimental side effects including
flu-like symptoms, liver damage, and depression. Moreover, common
bacterial and viral infections can elicit the activation of complex
endogenous inflammatory responses including robust IFNβ production.
These can be very debilitating and interfere with IFNβ treatment for MS.
Because IFNβ is
currently the best available therapy, it is critical to understand how the
effects of this mediator are regulated. There is no efficient way to
control the detrimental consequences of IFNβ exposure. This is a result
of the limited understanding of how the wide range of biological effects
induced by IFNβ are regulated, of how microbial products such as microbial
CpG-DNA induce a large amount of IFNβ and inflammatory cytokines, and of
how the context of endogenous responses to microbial products can modify
the consequences of IFNβ treatment. The goal of this project is to
address one of these issues by identifying the conditions that regulate
the positive and negative side effects of IFNβ. The results will provide
insights for developing approaches improving the therapeutic efficacy of
IFNβ. |
