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Increased macrophage chemoattractant protein-1 in cerebrospinal fluid precedes and predicts simian immunodeficiency
M C Zink1, G D Coleman, J L Mankowski
1Division of Comparative Medicine, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. m.czink@mail.jhmi.edu
Abstract:
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.
Insights
Macrophage chemoattractant protein-1 (MCP-1) elevation in cerebrospinal fluid (CSF) predicts brain inflammation in simian immunodeficiency virus (SIV) infection. The CSF:plasma MCP-1 ratio may indicate the risk of developing HIV-associated encephalitis.
Area of Science:
- Neuroimmunology
- Virology
- Pathology
Background:
- Macrophage chemoattractant protein-1 (MCP-1) is implicated in macrophage recruitment to the brain during human immunodeficiency virus (HIV) encephalitis.
- Understanding early markers of central nervous system (CNS) involvement in HIV infection is crucial for timely intervention.
Purpose of the Study:
- To investigate the role of MCP-1 levels in the cerebrospinal fluid (CSF) and plasma of macaques infected with simian immunodeficiency virus (SIV) as a potential predictor of encephalitis.
- To correlate MCP-1 levels with markers of neuroinflammation and neuropathology.
Main Methods:
- Simian immunodeficiency virus (SIV)-infected macaques were monitored for encephalitis development.
- Cerebrospinal fluid (CSF) and plasma MCP-1 levels were measured at various time points post-inoculation.
- Brain tissue was analyzed for MCP-1 expression, macrophage/microglia activation markers (CD68), and astrocyte activation markers (glial fibrillary acidic protein).
Main Results:
- Macaques with moderate-to-severe encephalitis showed significantly higher MCP-1 levels in CSF compared to plasma, detected early after inoculation and before brain lesions appeared.
- In contrast, macaques with minimal or no encephalitis maintained a constant CSF:plasma MCP-1 ratio.
- Increased CSF MCP-1 correlated with heightened expression of CD68, glial fibrillary acidic protein in white and gray matter, indicating macrophage/microglia and astrocyte activation.
Conclusions:
- The CSF:plasma MCP-1 ratio serves as a potential early prognostic marker for the development of HIV-induced CNS disease.
- Elevated MCP-1 in the CSF of SIV-infected macaques is associated with neuroinflammation and neuropathology.
- This ratio may aid in identifying individuals at risk for HIV encephalitis, enabling proactive management.