1. Artesunate Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Leukocyte Migration to the Central Nervous System.
- Author
-
Thomé R, de Carvalho AC, Alves da Costa T, Ishikawa LL, Fraga-Silva TF, Sartori A, de Oliveira AL, and Verinaud L
- Subjects
- Analysis of Variance, Animals, Artesunate, Brefeldin A pharmacology, Central Nervous System drug effects, Central Nervous System physiopathology, Cytokines metabolism, DNA-Binding Proteins deficiency, DNA-Binding Proteins genetics, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental immunology, Enzyme Inhibitors pharmacology, Female, Flow Cytometry, Gene Expression Regulation drug effects, Gene Expression Regulation genetics, Ionomycin pharmacology, Leukocytes physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Myelin-Oligodendrocyte Glycoprotein immunology, Myelin-Oligodendrocyte Glycoprotein toxicity, Peptide Fragments immunology, Peptide Fragments toxicity, Phorbol Esters pharmacology, Anti-Inflammatory Agents therapeutic use, Artemisinins therapeutic use, Cell Movement drug effects, Central Nervous System pathology, Encephalomyelitis, Autoimmune, Experimental drug therapy, Encephalomyelitis, Autoimmune, Experimental pathology, Leukocytes drug effects
- Abstract
Background and Aims: Experimental autoimmune encephalomyelitis (EAE) is T-cell-dependent disease of the central nervous system (CNS) of mice. This model resembles multiple sclerosis (MS) in many aspects. Therapies that focus in the modulation of the immune response and cellular infiltration in the CNS present best effects in the clinics. Artesunate (Art) is a semi-synthetic sesquiterpene derivative from artemisinin and has been shown to reduce the clinical signs of autoimmune disease models through mechanisms not yet understood. In this study, we aimed to evaluate whether administration of Art would ameliorate EAE., Methods and Results: C57BL6 mice were immunized with MOG35-55 peptide to induce EAE. At the same time, Art treatment started (3 mg/kg/day via i.p.) for five consecutive days. We found that Art treatment reduced the clinical signs of EAE and that correlated with a reduced infiltration of cells in the CNS. Disease amelioration did not correlate with immunomodulation as recall responses, leukocyte subpopulations, and gene expression analysis were similar among treated and untreated mice. Ultimately, further analysis provided data indicating that a possible mechanism of action for Art is dependent on the cellular migration to the CNS., Conclusions: Artesunate reduces the severity of EAE by inhibiting migration of pathogenic T cells to the CNS., (© 2016 John Wiley & Sons Ltd.)
- Published
- 2016
- Full Text
- View/download PDF