Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis
<p>Abstract</p> <p>Background</p> <p>Inhalational anesthetics have been shown to influence T cell functions both <it>in vitro</it> and <it>in vivo</it>, in many cases inducing T cell death, suggesting that exposure to these drugs could modify the...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-12-01
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| Series: | Journal of Neuroinflammation |
| Subjects: |
| _version_ | 1818808256608337920 |
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| author | Polak Paul E Dull Randall O Kalinin Sergey Sharp Anthony J Ripper Richard Weinberg Guy Schwartz David E Rubinstein Israel Feinstein Douglas L |
| author_facet | Polak Paul E Dull Randall O Kalinin Sergey Sharp Anthony J Ripper Richard Weinberg Guy Schwartz David E Rubinstein Israel Feinstein Douglas L |
| author_sort | Polak Paul E |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Inhalational anesthetics have been shown to influence T cell functions both <it>in vitro</it> and <it>in vivo</it>, 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.</p> <p>Methods</p> <p>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 <it>ex vivo</it> 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.</p> <p>Results</p> <p>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<sup>+</sup> 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.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-18T19:38:40Z |
| format | Article |
| id | doaj.art-8aff10aa519741d8b64148443911be80 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-18T19:38:40Z |
| publishDate | 2012-12-01 |
| publisher | BMC |
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| series | Journal of Neuroinflammation |
| spelling | doaj.art-8aff10aa519741d8b64148443911be802022-12-21T20:55:30ZengBMCJournal of Neuroinflammation1742-20942012-12-019127210.1186/1742-2094-9-272Sevoflurane reduces clinical disease in a mouse model of multiple sclerosisPolak Paul EDull Randall OKalinin SergeySharp Anthony JRipper RichardWeinberg GuySchwartz David ERubinstein IsraelFeinstein Douglas L<p>Abstract</p> <p>Background</p> <p>Inhalational anesthetics have been shown to influence T cell functions both <it>in vitro</it> and <it>in vivo</it>, 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.</p> <p>Methods</p> <p>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 <it>ex vivo</it> 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.</p> <p>Results</p> <p>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<sup>+</sup> 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.</p> <p>Conclusions</p> <p>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.</p>MyelinExperimental autoimmune encephalomyelitisInhaled anestheticMultiple sclerosis |
| spellingShingle | Polak Paul E Dull Randall O Kalinin Sergey Sharp Anthony J Ripper Richard Weinberg Guy Schwartz David E Rubinstein Israel Feinstein Douglas L Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis Journal of Neuroinflammation Myelin Experimental autoimmune encephalomyelitis Inhaled anesthetic Multiple sclerosis |
| title | Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis |
| title_full | Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis |
| title_fullStr | Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis |
| title_full_unstemmed | Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis |
| title_short | Sevoflurane reduces clinical disease in a mouse model of multiple sclerosis |
| title_sort | sevoflurane reduces clinical disease in a mouse model of multiple sclerosis |
| topic | Myelin Experimental autoimmune encephalomyelitis Inhaled anesthetic Multiple sclerosis |
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