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 influx of macrophages into the brain in human immunodeficiency virus (HIV) encephalitis. In this study, simian immunodeficiency virus-infected macaques that developed moderate-to-severe encephalitis had significantly higher MCP-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 contrast, CSF:plasma MCP-1 ratios remained constant at preinoculation levels in macaques that developed minimal or no encephalitis. Abundant MCP-1 protein and mRNA were detected in both macrophages and astrocytes in the brain. Macaques with increased MCP-1 in CSF had significantly greater expression of markers of macrophage and microglia activation and infiltration (CD68; P= .003) and astrocyte activation (glial fibrillary acidic protein; P= .019 and P= .031 in white and gray matter, respectively). The results suggest that the CSF:plasma MCP-1 ratio may be a valuable prognostic marker for the development of HIV-induced central nervous system disease.
Zink
M C
MC
Division of Comparative Medicine, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. m.czink@mail.jhmi.edu
Coleman
G D
GD
Mankowski
J L
JL
Adams
R J
RJ
Tarwater
P M
PM
Fox
K
K
Clements
J E
JE
D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D018932:Chemokine CCL2 / Q000097:blood / Q000134:cerebrospinal fluid* / Q000235:genetics; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000175:diagnosis*; D006801:Humans; D007150:Immunohistochemistry; D008251:Macaca; D011237:Predictive Value of Tests; D016097:Simian Acquired Immunodeficiency Syndrome / Q000134:cerebrospinal fluid* / Q000150:complications / Q000473:pathology; D015302:Simian Immunodeficiency Virus
D018932:Chemokine CCL2