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

J Neuroimmunol. 1994 Dec;55(2):143-52. doi: 10.1016/0165-5728(94)90004-3.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Viral / analysis
  • Demyelinating Diseases / etiology*
  • Demyelinating Diseases / pathology
  • Female
  • Hypersensitivity, Delayed
  • Interferon-gamma / analysis
  • Interferon-gamma / physiology*
  • Mice
  • T-Lymphocytes / immunology
  • Theilovirus* / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Interferon-gamma