MONOCLONAL ANTI-GAMMA INTERFERON ANTIBODIES ENHANCE EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

Interferon-gamma (IFN-gamma) is a cytokine with multiple activities on a variety of cells. Under various circumstances, IFN-gamma can exhibi t either pro-inflammatory or inhibitory actions. Treatment of SJL/J mi ce with a monoclonal antibody (Mab) to IFN-gamma during the afferent l imb of the immune response to myelin protein produced an enhancement o f acute experimental allergic encephalomyelitis (EAE), with increased morbidity, mortality and earlier onset of disease. Systemic administra tion of IFN-gamma did not improve or worsen clinical outcome, but dela yed disease onset. Passive transfer of immune lymph node cells co-acti vated with MBP and anti-IFN-gamma Mab resulted in more severe disease than that induced by MBP stimulated cells or MBP and IFN-gamma co-stim ulated cells. However, in vitro proliferation of an MBP specific T cel l line was not influenced by IFN-gamma nor anti-IFN-gamma treatment. M ab to IFN-gamma inhibited suppressor function, in a non-specific assay . These in vivo and in vitro results suggest that systemic IFN-gamma s erves as a physiological regulator of a suppressor mechanism in EAE. T he abrogation of this regulatory mechanism by anti-IFN-gamma administr ation contributes to a more severe form of experimental allergic encep halomyelitis.