CYTOKINES AND MURINE AUTOIMMUNE ENCEPHALOMYELITIS - INHIBITION OR ENHANCEMENT OF DISEASE WITH ANTIBODIES TO SELECT CYTOKINES, OR BY DELIVERY OF EXOGENOUS CYTOKINES USING A RECOMBINANT VACCINIA VIRUS SYSTEM

To examine the complex role of cytokines in the pathogenesis of active ly induced murine EAE we measured the levels of a number of cytokines (IL-6, IFN gamma and TNF) in the spinal cord and CSF of mice with acti ve experimental autoimmune encephalomyelitis (EAE) and found them all to be elevated. We next treated mice with antibodies to these three cy tokines, which were over expressed in the CNS, to determine if they wo uld alter disease and found the following: anti-IL-6 had no significan t effect on disease, anti-IFN gamma exacerbated disease, and anti-TNF either enhanced, had no effect or inhibited EAE depending on the antib ody used. We then treated mice with exogenous cytokines, delivered usi ng a recombinant vaccinia virus system, and found that the IL-6 and TN F virus constructs inhibited EAE whereas the IFN gamma construct had n o effect on disease. Other cytokine recombinant viruses were also test ed and it was found that the IL-1 beta, IL-2 and IL-10 viruses inhibit ed EAE while an IL-4 virus either had no effect or enhanced disease. W e do not know the mechanism of action of the various cytokines in this system, but irrespective of the mechanism(s), this work clearly demon strates that delivery of select cytokines using recombinant virus-cyto kine constructs can provide a powerful means of downregulating experim ental organ-specific autoimmune disease.