Increased macrophage chemoattractant protein-1 in cerebrospinal fluid precedes and predicts simian immunodeficiency virus encephalitis

Macrophage chemoattractant protein-1 (MCP-1) may be a key trigger for the i nflux of macrophages into the brain in human immunodeficiency virus (HIV) e ncephalitis. In this study, simian immunodeficiency virus-infected macaques that developed moderate-to-severe encephalitis had significantly higher MC P-1 levels in cerebrospinal fluid (CSF) than in plasma as early as 28 days after inoculation, which was before the development of brain lesions. In co ntrast, CSF:plasma MCP-1 ratios remained constant at preinoculation levels in macaques that developed minimal or no encephalitis. Abundant MCP-1 prote in and mRNA were detected in both macrophages and astrocytes in the brain. Macaques with increased MCP-1 in CSF had significantly greater expression o f markers of macrophage and microglia activation and infiltration (CD68; P = .003) and astrocyte activation (glial fibrillary acidic protein; P = .019 and P = .031 and in white and gray matter, respectively). The results sugg est that the CSF:plasma MCP-1 ratio may be a valuable prognostic marker for the development of HIV-induced central nervous system disease.