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Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis

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Title: Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis
Author(s): Polak, Paul E.; Dull, Randall O.; Kalinin, Sergey; Sharp, Anthony J.; Ripper, Richard; Weinberg, Guy; Schwartz, David E.; Rubinstein, Israel; Feinstein, Douglas L.
Subject(s): Myelin Experimental autoimmune encephalomyelitis Inhaled anesthetic multiple sclerosis
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)gamma. 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 IFN gamma 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.
Issue Date: 2012-12
Publisher: BioMed Central
Citation Info: Polak, P. E., Dull, R. O., Kalinin, S., Sharp, A. J., Ripper, R., Weinberg, G., Schwartz, D. E., Rubinstein, I. and Feinstein, D. L. Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis. Journal of Neuroinflammation. 2012. 9. DOI: 10.1186/1742-2094-9-272
Type: Article
Description: © 2012 Polak et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
URI: http://hdl.handle.net/10027/12822
ISSN: 1742-2094
Sponsor: This work was funded in part by grants from the National Multiple Sclerosis Society (DLF) and the Department of Veterans Affairs (DLF, GW).
Date Available in INDIGO: 2014-03-18
 

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