Reduction in glial immunity and neuropathology by a PAF antagonist and an MMP and TNF alpha inhibitor in SCID mice with HIV-1 encephalitis

The effects of anti-inflammatory drugs on glial immunity and neuropathology were determined in a severe combined immune deficiency (SCID) mouse model of HIV-1 encephalitis. HIV-l-infected human monocyte-derived macrophages (M DM) are stereotactically inoculated into basal ganglia resulting in a multi nucleated giant cell encephalitis. A platelet activating factor antagonist and a matrix metalloproteinase inhibitor, which also inhibits tumor necrosi s factor alpha release, were administered to animals at the time of the MDM inoculation. The drugs administered in combination markedly reduced brain inflammation, astrogliosis and microglia activation. These findings demonst rate that reduction of brain inflammatory responses, independent of viral r eplication, can affect HIVE pathology in an animal model system of disease. (C) 2001 Elsevier Science B.V. All rights reserved.