Inducible nitric oxide synthase (iNOS) expression correlates with disease activity in adoptively-transferred experimental autoimmune encephalomyelitis (EAE)

EAE is an autoimmune inflammatory CNS demyelinating disorder which is often used as a model for multiple sclerosis The present study was undertaken to determine whether increased iNOS enzyme activity and iNOS mRNA correlate with the activity or clinical severity of murine EAE mRNA encoding iNOS was measured by competitive reverse transcriptase polymerase chain reaction (cRT-PCR) and ribonuclease protection assays (RPA) in spinal cords of EAE-affected and control mice Levels of iNOS mRNA were increased in spinal cords of mice with acute EAE using both methods of assay, with a 10 to 40-fold increase in iNOS message in EAEaffected versus normal spinal cords. iNOS enzyme activity was assayed by conversion of 3H-L-arginine into L-citrulline in the absence of calcium. iNOS enzyme activity was increased in spinal cords of mice with clinically active EAE, and was greatest during early acute illness. iNOS enzyme activity was not increased during stable, chronic disease Immunoreactivity to iNOS was detected in cells of astrocytic morphology in sections of spinal cords from mice with acute EAE. The correlation of iNOS expression with active disease in acute EAE suggests a potential pathogenic role for NO in this model of cell-mediated CNS autoimmunity.