Monoclonal Anti-Gamma Interferon Antibodies Enhance Experimental Allergic Encephalomyelitis

Interferon-γ (IFN-γ) is a cytokine with multiple activities on a variety of cells. Under various circumstances, IFN-γ can exhibit either pro-inflammatory or inhibitory actions. Treatment of SJL/J mice with a monoclonal antibody (Mab) to IFN-γ during the afferent limb of the immune response to myelin protein produced an enhancement of acute experimental allergic encephalomyelitis (EAE), with increased morbidity, mortality and earlier onset of disease. Systemic administration of IFN-γ did not improve or worsen clinical outcome, but delayed disease onset. Passive transfer of immune lymph node cells co-activated with MBP and anti-IFN-γ Mab resulted in more severe disease than that induced by MBP stimulated cells or MBP and IFN-γ co-stimulated cells. However, in vitro proliferation of an MBP specific T cell line was not influenced by IFN-γ nor anti-IFN-γ treatment. Mab to IFN-γ inhibited suppressor function, in a non-specific assay. These in vivo and in vitro results suggest that systemic IFN-γ serves as a physiological regulator of a suppressor mechanism in EAE. The abrogation of this regulatory mechanism by anti-IFN-γ administration contributes to a more severe form of experimental allergic encephalomyelitis.