ABSTRACT
The central nervous system (CNS) has long been viewed as an immunologically privileged and isolated organ beyond the reach of immune system and its components. This immunoseparation is established and maintained through the presence of the unique structure of the blood-brain barrier and CNS immunosuppressive milieu. However, during pathogenesis of HIV-1-associated dementia and multiple sclerosis, both immune-mediated diseases, macrophage/microglia (MØ), and astrocytes participate in destruction, protection, and attempted repair of the CNS. Complicated pathogenesis of these two dementing and disabling diseases involves activation and interaction of MØ, astrocytes, and Th1-and Th2-T lymphocytes. Expression of MHC and adhesion molecules and release of various reactive oxygen/nitrogen intermediates, quinolinic acid, chemokines, cytokines, and other components of inflammation are the consequences of these inflammatory cascades. The role of MØ and astrocytes in cellular/molecular mechanisms of pathogenesis HAD and MS are examined and reviewed. HIV-1 infection is the original insult in HAD, and macrophages are involved in CNS invasion by HIV-1. The etiology of MS remains unknown, and MØ are involved
in loss of myelin/oligodendrocyte complex. Astrocytes are also activated in pathogenesis of HAD and MS. In both diseases, cytokine/chemokine communication between microglia, astrocytes, and Th1-and Th2-T lymphocytes occurs and leads to both destruction and attempted repair of the CNS.
