Failure of treatment with Linomide or oral myelin tolerization to ameliorate demyelination in a viral model of multiple sclerosis

Kristen M. Drescher, Cynthia Rivera-Quinones, Claudia F. Lucchinetti, Moses Rodriguez

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Both Linomide (quinoline-3-carboxamide) and tolerization with self- antigens have been demonstrated to successfully ameliorate demyelinating disease in experimental autoimmune encephalomyelitis (EAE). Based on the autoimmune hypothesis of multiple sclerosis (MS), both agents have been tested in clinical trials but have been found to be toxic or not efficacious. We investigated the efficacy of these immunomodulators in an alternative experimental model of MS, a virus-induced demyelinating disease. Oral administration of Linomide to Theiler's virus-infected mice beginning either at time of infection or at day 15 post-infection (p.i.) resulted in an increased percentage of spinal cord quadrants with demyelination. Administration of Linomide beginning at day 15 p.i. increased lesion size as compared to infected control-treated mice. Treatment with 80 mg kg-1 day- 1 of Linomide beginning at the time of infection significantly increased the number of Theiler's murine encephalomyelitis virus (TMEV)-positive cells mm- 2 of spinal cord white matter. There were no differences in the amount of remyelination between mice treated with Linomide or water. However, chronically infected mice treated with Linomide had severely reduced spontaneous vertical activity as measured using a activity wheel. Oral tolerization of mice with mouse or bovine myelin had no effect on virus- induced demyelination or virus antigen expression. The contrasting results obtained between the TMEV model and the autoimmune model of demyelination do not support recent reports suggesting that the underlying mechanism of demyelination in the Theiler's model is autoimmune.

Original languageEnglish
Pages (from-to)111-119
Number of pages9
JournalJournal of Neuroimmunology
Volume88
Issue number1-2
DOIs
StatePublished - Aug 1 1998
Externally publishedYes

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Demyelinating Diseases
Myelin Sheath
Treatment Failure
Multiple Sclerosis
Theilovirus
Viruses
Infection
Spinal Cord
Autoimmune Experimental Encephalomyelitis
Poisons
Autoantigens
Immunologic Factors
Oral Administration
roquinimex
Theoretical Models
Clinical Trials
Antigens
Water

All Science Journal Classification (ASJC) codes

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

Failure of treatment with Linomide or oral myelin tolerization to ameliorate demyelination in a viral model of multiple sclerosis. / Drescher, Kristen M.; Rivera-Quinones, Cynthia; Lucchinetti, Claudia F.; Rodriguez, Moses.

In: Journal of Neuroimmunology, Vol. 88, No. 1-2, 01.08.1998, p. 111-119.

Research output: Contribution to journalArticle

Drescher, Kristen M. ; Rivera-Quinones, Cynthia ; Lucchinetti, Claudia F. ; Rodriguez, Moses. / Failure of treatment with Linomide or oral myelin tolerization to ameliorate demyelination in a viral model of multiple sclerosis. In: Journal of Neuroimmunology. 1998 ; Vol. 88, No. 1-2. pp. 111-119.
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