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 syndrome (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 immunodeficiency 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 log(10) 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 log(10) 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.