title: Artesunate Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Leukocyte Migration to the Central Nervous System.
abstract: 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.
  
  
  
  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.
  
  
  
  Artesunate reduces the severity of EAE by inhibiting migration of pathogenic T cells to the CNS.
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Thomé
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: de Carvalho
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Alves da Costa
authors.affiliation: Department of Immunology and Microbiology, Institute of Biosciences of Botucatu, São Paulo State University, Botucatu, Brazil.
authors.forename: Larissa Lumi Watanabe
authors.initials: LL
authors.lastname: Ishikawa
authors.affiliation: Department of Immunology and Microbiology, Institute of Biosciences of Botucatu, São Paulo State University, Botucatu, Brazil.
authors.forename: Thais Fernanda de Campos
authors.initials: TF
authors.lastname: Fraga-Silva
authors.affiliation: Department of Immunology and Microbiology, Institute of Biosciences of Botucatu, São Paulo State University, Botucatu, Brazil.
authors.forename: Alexandrina
authors.initials: A
authors.lastname: Sartori
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Alexandre Leite Rodrigues
authors.initials: AL
authors.lastname: de Oliveira
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, Brazil.
authors.forename: Liana
authors.initials: L
authors.lastname: Verinaud
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D020126:Brefeldin A / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D015759:Ionomycin / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology / Q000633:toxicity; D010446:Peptide Fragments / Q000276:immunology / Q000633:toxicity; D010703:Phorbol Esters / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D037621:Artemisinins; D016207:Cytokines; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010703:Phorbol Esters; C499308:Rag2 protein, mouse; C445081:myelin oligodendrocyte glycoprotein (35-55); D020126:Brefeldin A; C119222:phorbol-12-myristate; D015759:Ionomycin; D000077332:Artesunate
keywords: Artesunate; Cellular migration; Experimental autoimmune encephalomyelitis; Neuroinflammation