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

Autor: de Oliveira DM; Neuroimmune Interactions Laboratory, Department of Immunology, University of São Paulo, São Paulo, SP, 05508-900, Brazil. daniel-larissa@hotmail.com.; Laboratory for Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Science IV, University of São Paulo (USP), São Paulo, SP, 05508-090, Brazil. daniel-larissa@hotmail.com., de Oliveira EM; Discipline of Clinical Neurology, Federal University of São Paulo UNIFESP, São Paulo, SP, 04023-900, Brazil., Ferrari Mde F; Department of Genetics and Evolutive Biology, Biosciences Institute, University of São Paulo (USP), São Paulo, SP, 05508-090, Brazil., Semedo P; Biosciences Institute, University of São Paulo, São Paulo, SP, 05508-900, Brazil., Hiyane MI; Laboratory for Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Science IV, University of São Paulo (USP), São Paulo, SP, 05508-090, Brazil., Cenedeze MA; Laboratory of Clinical and Experimental Immunology, Nephrology Division, Medicine Department, Federal University of São Paulo UNIFESP, São Paulo, SP, 04023-900, Brazil., Pacheco-Silva A; Laboratory of Clinical and Experimental Immunology, Nephrology Division, Medicine Department, Federal University of São Paulo UNIFESP, São Paulo, SP, 04023-900, Brazil., Câmara NO; Laboratory of Clinical and Experimental Immunology, Nephrology Division, Medicine Department, Federal University of São Paulo UNIFESP, São Paulo, SP, 04023-900, Brazil.; Laboratory for Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Science IV, University of São Paulo (USP), São Paulo, SP, 05508-090, Brazil., Peron JP; Neuroimmune Interactions Laboratory, Department of Immunology, University of São Paulo, São Paulo, SP, 05508-900, Brazil.
Jazyk: angličtina
Zdroj: Inflammopharmacology [Inflammopharmacology] 2015 Dec; Vol. 23 (6), pp. 343-54. Date of Electronic Publication: 2015 Nov 11.
DOI: 10.1007/s10787-015-0252-1
Abstrakt: 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.
Databáze: MEDLINE
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