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01-12-2015 | Research Article

Simvastatin ameliorates experimental autoimmune encephalomyelitis by inhibiting Th1/Th17 response and cellular infiltration

Authors: Daniel May de Oliveira, Enedina Maria Lobato de Oliveira, Merari de Fátima Ramires Ferrari, Patrícia Semedo, Meire Ioshie Hiyane, Marcos Antônio Cenedeze, Alvaro Pacheco-Silva, Niels Olsen Saraiva Câmara, Jean Pierre Schatzmann Peron

Published in: Inflammopharmacology | Issue 6/2015

Abstract

Aim

Experimental autoimmune encephalomyelitis (EAE) is a CD4⁺-mediated autoimmune pathology of the central nervous system (CNS) that is used as a model for the study of the human neuroinflammatory disease, multiple sclerosis. During the development of EAE, auto-reactive Th1 and Th17 CD4⁺ T cells infiltrate the CNS promoting inflammatory cells recruitment, focal inflammation and tissue destruction. In this sense, statins, agents used to lower lipid levels, have recently shown to exert interesting immunomodulatory function. In fact, statins promote a bias towards a Th2 response, which ameliorates the clinical outcome of EAE. Additionally, simvastatin can inhibit Th17 differentiation. However, many other effects exerted on the immune system by statins have yet to be clarified, in particular during neuroinflammation. Thus, the aim of this study was to investigate the effects of simvastatin on the development of experimental autoimmune encephalomyelitis.

Methods

Mice were immunized with MOG_35–55 and EAE severity was assessed daily and scored using a clinical scale. Cytokine secretion by mononuclear cells infiltrating the CNS was evaluated by flow cytometry.

Results

Simvastatin (5 mg/kg/day) improved clinical outcome, induced an increase in TGF-β mRNA expression and inhibited IL-6, IL-12p40, IL-12p70, RANTES and MIP-1β secretion (p < 0.05). This was accompanied by a significant decrease in CNS inflammatory mononuclear cell infiltration, with reduced frequencies of both Th1 and Th17 cells. Simvastatin inhibited the proliferation of T lymphocytes co-cultured with primary microglial cells.

Conclusions

Simvastatin treatment promotes EAE clinical amelioration by inhibiting T cell proliferation and CNS infiltration by pathogenic Th1 and Th17 cells.

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Title: Simvastatin ameliorates experimental autoimmune encephalomyelitis by inhibiting Th1/Th17 response and cellular infiltration
Authors: Daniel May de Oliveira
Enedina Maria Lobato de Oliveira
Merari de Fátima Ramires Ferrari
Patrícia Semedo
Meire Ioshie Hiyane
Marcos Antônio Cenedeze
Alvaro Pacheco-Silva
Niels Olsen Saraiva Câmara
Jean Pierre Schatzmann Peron
Publication date: 01-12-2015
Publisher: Springer International Publishing
Published in: Inflammopharmacology / Issue 6/2015
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-015-0252-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Simvastatin ameliorates experimental autoimmune encephalomyelitis by inhibiting Th1/Th17 response and cellular infiltration

Abstract

Aim

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Aim

Methods

Results

Conclusions

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