Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis

Paul E. Polak, Randall O. Dull, Sergey Kalinin, Anthony J. Sharp, Richard Ripper, Guy Weinberg, David E. Schwartz, Israel Rubinstein, Douglas L. Feinstein

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background: Inhalational anesthetics have been shown to influence T cell functions both in vitro and in vivo, in many cases inducing T cell death, suggesting that exposure to these drugs could modify the course of an autoimmune disease. We tested the hypothesis that in mice immunized to develop experimental autoimmune encephalomyelitis (EAE), a well established model of multiple sclerosis (MS), treatment with the commonly used inhalational anesthetic sevoflurane would attenuate disease symptoms.Methods: C57Bl6 female mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide residues 35 to 55 to induce a chronic demyelinating disease. At day 10 after immunization, the mice were subjected to 2 h of 2.5% sevoflurane in 100% oxygen, or 100% oxygen, alone. Following treatment, clinical scores were monitored up to 4 weeks, after which brain histology was performed to measure the effects on astrocyte activation and lymphocyte infiltration. Effects of sevoflurane on T cell activation were studied using splenic T cells isolated from MOG peptide-immunized mice, restimulated ex vivo with MOG peptide or with antibodies to CD3 and CD28, and in the presence of different concentrations of sevoflurane. T cell responses were assessed 1 day later by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for proliferation, lactate dehydrogenase (LDH) release for cell death, and inflammatory activation by production of interleukin (IL)-17 and interferon (IFN)γ.Results: Clinical scores in the oxygen-treated group increased until day 28 at which time they showed moderate to severe disease (average clinical score of 2.9). In contrast, disease progression in the sevoflurane-treated group increased to 2.1 at day 25, after which it remained unchanged until the end of the study. Immunohistochemical analysis revealed reduced numbers of infiltrating leukocytes and CD4+ cells in the CNS of the sevoflurane-treated mice, as well as reduced glial cell activation. In splenic T cells, low doses of sevoflurane reduced IFNγ production, cell proliferation, and increased LDH release.Conclusions: These results are the first to show attenuation of EAE disease by an inhaled anesthetic and are consistent with previous reports that inhaled anesthetics, including sevoflurane, can suppress T cell activation that, in the context of autoimmune diseases such as MS, could lead to reduced clinical progression.

Original languageEnglish (US)
Article number272
JournalJournal of Neuroinflammation
Volume9
DOIs
StatePublished - Dec 19 2012
Externally publishedYes

Keywords

  • Experimental autoimmune encephalomyelitis
  • Inhaled anesthetic
  • Multiple sclerosis
  • Myelin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis'. Together they form a unique fingerprint.

  • Cite this

    Polak, P. E., Dull, R. O., Kalinin, S., Sharp, A. J., Ripper, R., Weinberg, G., Schwartz, D. E., Rubinstein, I., & Feinstein, D. L. (2012). Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis. Journal of Neuroinflammation, 9, [272]. https://doi.org/10.1186/1742-2094-9-272