Macrophage chemoattractant protein-1 levels in cerebrospinal fluid correlate with containment of JC virus and prognosis of acquired immunodeficiency syndrome–associated progressive multifocal leukoencephalopathy

Abstract

In the highly active antiretroviral therapy (HAART) era, the role of the inflammatory response in acquired immunodeficiency syndrom (AIDS)-related progressive multifocal leukoencephalopathy (PML) remains controversial. In this study, JC virus DNA load and levels of cytokines were determined in cerebrospinal fluid (CSF) from 32 human immunodeficency virus (HIV)-1–infected patients with confirmed PML who underwent HAART; cytokines were also measured in 12 HIV-positive controls. Predictors of survival were analyzed by Cox's models. Macrophage chemoattractant protein (MCP)-1 levels were significantly higher in PML patients than in controls (mean ± SD, 2.45 ± 0.64 versus 1.32 ± 0.64 log₁₀ pg/ml, P < .0001). In PML patients, the higher concentration of MCP-1 correlated with lower JC viral load (r = −.405, P = .036). Higher concentrations of MCP-1 in CSF were associated with longer survival on HAART after adjusting for CD4 counts (for each log₁₀ pg/ml higher, hazard ratio for death 0.28, 95% confidence interval 0.08–1.00). Predictors of shorter survival were lower baseline CD4 counts, higher JCV DNA concentrations, lower Karnofsky, and no prior HAART exposure. These results showed that higher CSF levels of MCP-1, an inflammatory cytokine, were correlated with better prognosis in HAART-treated patients with PML.

Keywords:

• AIDS
• cerebrospinal fluid
• JC virus
• MCP-1
• progressive multifocal leukoencephalopathy
• viral load

This work has been presented in part at the HIV Molecular and Clinical Neuroscience Workshop and 5th International Symposium of Neurovirology, Baltimore, Maryland, 2–6 September 2003 (abstract number I 99); and at the 11th Conference on Retrovirus and Opportunistic Infections, San Francisco, California, 8–11 February 2004 (abstract number 506). Informed consent was obtained from subjects in accordance with guidelines of the local institutions where the study was conducted. The authors of this manuscript do not have commercial or other association that might pose a conflict of interest. This work was supported by Italian National Institute of Health, IV Progetto Nazionale AIDS–Infezioni Opportunistiche e Tubercolosi, grant number 50D.7. Received 2 December 2004; accepted 6 December 2004.