Alteration in the level of interferon-γ results in acceleration of Theiler's virus-induced demyelinating disease
article
Intracerebral (i.c.) inoculation of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in immune-mediated demyelination. We examined the role of interferon (IFN)-γ in this virally induced pathogenesis. Intraperitoneal (i.p.) injection of susceptible mice with an IFN-γ-neutralizing monoclonal antibody (mAb), DB-1, resulted in a significantly accelerated onset of disease. The anti-IFN-γ mAb-treated animals showed a strong delayed-type hypersensivity (DTH) response to the virus similar to that of control mAb-treated animals. Treatment with anti-IFN-γ mAb appeared to decrease TMEV-specific mAb titers in one of the protocols used. Intracerebral injection of the anti-IFN-γ mAb had no significant effect on the clinical course of disease. However, intracerebral administration of recombinant IFN-γ significantly accelerated the onset of TMEV-induced disease, as well as enhanced TMEV-specific T cell proliferation and DTH responses. The enhancing effect of IFN-γ was completely abrogated by simultaneous treatment with anti-IFN-γ mAb. Collectively, our data suggest that the level of IFN-γ plays a key role in the TMEV-induced inflammatory response and a perturbation of this balance may result in an alteration in the course of the demyelinating disease.
Topics
Gamma interferonMonoclonal antibodyAnimal experimentAnimal modelDelayed hypersensitivityDemyelinating diseaseEnzyme linked immunosorbent assayFemaleHistologyLymphocyte proliferationMouseMurine encephalomyelitis virusNonhumanPriority journalT lymphocyteAnimalAntibodies, MonoclonalAntibodies, ViralDemyelinating DiseasesFemaleHypersensitivity, DelayedInterferon Type IIMiceSupport, U.S. Gov't, P.H.S.T-LymphocytesTheilovirus82115-62-6
TNO Identifier
232800
ISSN
01655728
Source
Journal of Neuroimmunology, 55(2), pp. 143-152.
Pages
143-152
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