Alteration in the level of interferon-gamma 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)-gamma in this virally induced pathogenesis. Intraperitoneal (i.p.) injection of susceptible mice with an IFN-gamma-neutralizing monoclonal antibody (mAb), DB-1, resulted in a significantly accelerated onset of disease. The anti-IFN-gamma 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-gamma mAb had no significant effect on the clinical course of disease. However, intracerebral administration of recombinant IFN-gamma 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-gamma was completely abrogated by simultaneous treatment with anti-IFN-gamma mAb. Collectively, our data suggest that the level of IFN-gamma 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.
Pullen
L C
LC
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611.
Miller
S D
SD
Dal Canto
M C
MC
Van der Meide
P H
PH
Kim
B S
BS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000032:analysis; D003711:Demyelinating Diseases / Q000209:etiology* / Q000473:pathology; D005260:Female; D006968:Hypersensitivity, Delayed; D007371:Interferon-gamma / Q000032:analysis / Q000502:physiology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology; D017945:Theilovirus / Q000276:immunology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D007371:Interferon-gamma