Local neurochemicals and site-specific immune regulation in the CNS

Although it is often described as "immunologically privileged," the brain c an display vigorous immune activity, both clinically and experimentally. Th e underlying control mechanisms are under active study. Here we shift atten tion from the brain as a whole to its diverse microenvironments. We review evidence that immune regulation in the brain is site-specific, and that loc al neurochemicals contribute to the site-specific control. Key points are i llustrated by recent work from a rat model in which local injection of the proinflammatory cytokine, IFN-gamma, was used to modulate 2 essential aspec ts of the cell-mediated immune response: T cell entry from the blood, and e xpression of the MHC proteins that are needed to present antigen to the new ly entered T cells. A growing number of neurologic disorders are known to b e exacerbated by the immune/inflammatory network. Understanding the factors that influence local immune function may help explain the distribution of localized CNS damage and, more importantly, may suggest new therapeutic app roaches for both desirable and unwanted responses.