The effects of ovine interferon-[] treatment on Theiler's virus-induced demyelination in female SJL/J mice /
Theiler's murine encephalomyelitis virus (TMEV) is a picornavirus that is used as an animal model for the study of multiple sclerosis (MS). One of the current therapies for MS involves the administration of a type I interferon, IFN-β. The administration of IFN-β can result in unfavored, psych...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
2001.
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| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=725922231&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | Theiler's murine encephalomyelitis virus (TMEV) is a picornavirus that is used as an animal model for the study of multiple sclerosis (MS). One of the current therapies for MS involves the administration of a type I interferon, IFN-β. The administration of IFN-β can result in unfavored, psychological side-effects including clinical depression. A second type I interferon, ovine IFN-[t], has previously been found to be less cytotoxic than IFN-β. This study focuses on the effects of IFN-[t] on SJL/J mice at 0 months, 2 months, and 4 months post-infection with TMEV strain BeAn. Through neurological exams and histological analysis of the CNS, we report that IFN-[t] administration significantly reversed the neurological abnormalities induced by TMEV infection when given at 4 months post-infection. Histologically, treatment at 4 months post-infection resulted in a significant decrease in lesion occurrence in the ventral and dorsal funiculi of the spinal cord. Inflammation and demyelination were both reduced as measured via percent area affected in hemotoxylin + eosin stained and myelin oligodendrocyte glycoprotein-specific immunostained spinal cord sections embedded in paraffin. No effect was detected with treatment at 2 months post-infection. In contrast, SJL/J mice pretreated with IFN-[t] displayed increased disease progression when compared to controls, as well as increased lesion development. Treatment with IFN-[t] from 4 to 6 months post-infection resulted in an increase in serum IL-10 levels, increase in IL-1, IL-6, IL-10, and IFN-γ mRNA in the spinal cord, and a decrease in delayed-type hypersensitivity response to myelin membrane when compared to saline treated, infected controls. No significant change was noted in white blood cell differential between IFN-[t] or saline treated infected animals. In conclusion, it is proposed that IFN-[t] mediates its therapeutic effects by upregulating IL-10, which suppresses delayed-type hypersensitivity responses, thereby inhibiting the inflammatory demyelinating process. IFN-[t] may be a useful therapeutic agent in the treatment of multiple sclerosis. |
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| Item Description: | Vita. "Major Subject: Veterinary Anatomy". In title symbols are used. |
| Physical Description: | xv, 234 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilm Inc. |
| Bibliography: | Includes bibliographical references (leaves 156-191). |