The influence of glatiramer acetate on Th17-immune response in multiple sclerosis.

Mikhail Melnikov,Vladimir Rogovskii,Alexey Boyko,Mikhail Pashenkov,Anastasiya Sviridova,Nina Murugina,Svetlana Sharanova,Yulia Dagil,Tatiana Ospelnikova,Anna Nikolaeva,Vladimir Murugin,Jagadeesh Bayry

doi:10.1371/journal.pone.0240305

Mikhail Melnikov, Vladimir Rogovskii + Show 10 more

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https://doi.org/10.1371/journal.pone.0240305

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Abstract

Glatiramer acetate (GA) is approved for the treatment of multiple sclerosis (MS). However, the mechanism of action of GA in MS is still unclear. In particular, it is not known whether GA can modulate the pro-inflammatory Th17-type immune response in MS. We investigated the effects of original GA (Copaxone®, Teva, Israel) and generic GA (Timexone®, Biocad, Russia) on Th17- and Th1-type cytokine production in vitro in 25 patients with relapsing-remitting MS and 25 healthy subjects. Both original and generic GA at concentrations 50–200 μg/ml dose-dependently inhibited interleukin-17 and interferon-γ production by anti-CD3/anti-CD28-activated peripheral blood mononuclear cells from MS patients and healthy subjects. This effect of GA was reproduced using purified CD4+ T cells, suggesting that GA can directly modulate the functions of Th17 and Th1 cells. At high concentrations (100–200 μg/ml), GA also suppressed the production of Th17-differentiation cytokines (interleukin-1β and interleukin-6) by lipopolysaccharide (LPS)-activated dendritic cells (DCs). These GA/LPS-treated DCs induced lower interleukin-17 and interferon-γ production by autologous CD4+ T cells compared to LPS-treated DCs. These data suggest that GA can inhibit Th17-immune response and that this inhibitory effect is preferentially exercised by direct influence of GA on T cells. We also demonstrate a comparable ability of original and generic GA to modulate pro-inflammatory cytokine production.

Highlights

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS) with the autoimmune mechanism of development.Glatiramer acetate (GA) is approved for the treatment of relapsing forms of MS as a first-line therapy [1]
To clarify the effect of GA on T cells, we investigated the expression of IL-17, IFN-γ and IL-10 mRNA in CD4+ T cells stimulated by anti-CD3/anti-CD28 microbeads in the presence of generic or original GA at concentrations of 50 μg/ml, 100 μg/ml and 200 μg/ml
Glatiramer acetate is one of the first therapeutics approved for treatment of relapsing-remitting MS

Summary

Introduction

Glatiramer acetate (GA) (previously known as copolymer 1) is approved for the treatment of relapsing forms of MS as a first-line therapy [1]. The influence of glatiramer acetate on Th17-cells grants from Biocad, Generium, Janssen and Merck Serono. Svetlana Sharanova has received honoraria for participation in clinical trials from Actelion, Biocad, Generium, Anastsiya Sviridova has received honoraria for participation in clinical trials from Biocad. Alexey Boyko has received speakers honoraria and/or research grants from Bayer, Biocad, Biogen, Generium, Merck Serono, Novartis, Rosche, Sanofi and Teva. The authors state that this does not alter their adherence to all the PLOS ONE policies on sharing data and materials

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