INDUCIBLE NITRIC-OXIDE SYNTHASE GENE-EXPRESSION AND ENZYME-ACTIVITY CORRELATE WITH DISEASE-ACTIVITY IN MURINE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Messenger RNA encoding inducible NO synthase (iNOS) was measured by co mpetitive reverse transcriptase polymerase chain reaction (cRT-PCR) an d ribonuclease protection assays in spinal cords from mice at varying stages of experimental allergic encephalomyelitis (EAE) and from contr ol mice. iNOS mRNA was increased in spinal cords from mice with acute EAE. cRT-PCR assays revealed a 10-20-fold increase in iNOS mRNA in spi nal cords during acute EAE compared with the level observed in normal mouse spinal cords. Functional iNOS activity, as assessed by assay of calcium-independent citrulline production, was also significantly incr eased in spinal cords from mice with acute EAE in comparison to normal controls. The correlation of functional iNOS expression with active d isease in EAE is consistent with a pathogenic role for excess NO in th is model of cell-mediated central nervous system autoimmunity.