@article{
author = "Miljković, Đorđe and Blaževski, Jana and Petković, Filip and Nikolovski, Neda and Momčilović, Miljana and Stanisavljević, Suzana and Jevtić, Bojan and Stojkovic, Marija Mostarica and Spasojevic, Ivan",
year = "2015",
abstract = "Dimethyl fumarate (DMF), a new drug for multiple sclerosis (MS)
treatment, acts against neuroinflammation via mechanisms that are
triggered by adduct formation with thiol redox switches. Ethyl pyruvate
(EP), an off-the-shelf agent, appears to be a redox analog of DMF, but
its immunomodulatory properties have not been put into the context of MS
therapy. In this article, we examined and compared the effects of EP and
DMF on MS-relevant activity/functions of T cells, macrophages,
microglia, and astrocytes. EP efficiently suppressed the release of MS
signature cytokines, IFN-gamma and IL-17, from human PBMCs. Furthermore,
the production of these cytokines was notably decreased in
encephalitogenic T cells after in vivo application of EP to rats.
Production of two other proinflammatory cytokines, IL-6 and TNF, and NO
was suppressed by EP in macrophages and microglia. Reactive oxygen
species production in macrophages, microglia activation, and the
development of Ag-presenting phenotype in microglia and macrophages were
constrained by EP. The release of IL-6 was reduced in astrocytes.
Finally, EP inhibited the activation of transcription factor NF-kappa B
in microglia and astrocytes. Most of these effects were also found for
DMF, implying that EP and DMF share common targets and mechanisms of
action. Importantly, EP had in vivo impact on experimental autoimmune
encephalomyelitis, an animal model of MS. Treatment with EP resulted in
delay and shortening of the first relapse, and lower clinical scores,
whereas the second attack was annihilated. Further studies on the
possibility to use EP as an MS therapeutic are warranted.",
journal = "Journal of Immunology",
title = "A Comparative Analysis of Multiple Sclerosis-Relevant Anti-Inflammatory
Properties of Ethyl Pyruvate and Dimethyl Fumarate",
number = "6",
volume = "194",
doi = "10.4049/jimmunol.1402302",
pages = "2493-2503"
}
