Protection of myelin basic protein immunized mice from free-radical mediated inflammatory cell invasion of the central nervous system by the natural peroxynitrite scavenger uric acid

Peroxynitrite (ONOO-), the product of nitric oxide (NO.) and superoxide (O- 2(-.)), is believed to be a major contributor to immunotoxicity when produc ed by activated cells expressing inducible nitric oxide synthase (iNOS). Ur ic acid (UA) is a natural scavenger of ONOO- that is present at high levels in the sera of humans and other higher order primates relative to most low er mammals. We have previously shown that UA treatment is therapeutic in ex perimental allergic encephalomyelitis (EAE), a rodent model of multiple scl erosis (MS). In this study we have examined the effect of UA therapy on the dynamics of the appearance of iNOS-positive cells in central nervous syste m (CNS) tissue of mice subjected to the stimuli that cause EAE. The results indicate that UA prevents activated monocytes from entering CNS tissue whe re they may contribute to the pathogenesis of MS and other CNS diseases. (C ) 2000 Elsevier Science Ireland Ltd. All rights reserved.