Alteration in the level of interferon-γ results in acceleration of Theiler's virus-induced demyelinating disease

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 hypersensitivity (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 IF-γ plays a key role in the TMEV-induced inflammatory respopnse and a perturbation of this balance may result in an alteration in the course of the demyelinating disease.