Cerebrospinal fluid beta chemokine concentrations in neurocognitively impaired individuals infected with human immunodeficiency virus type 1

Macrophages express the chemokine receptor CCR-5, a coreceptor for human im munodeficiency virus (HIV) entry. This receptor is ligated by beta chemokin es, which influence HIV type 1 (HIV-1) replication in CCR-5-bearing cells i n vitro and could influence the course of infection in the central nervous system. Cerebrospinal fluid (CSF) samples from 73 HIV-infected men were ass ayed for macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and regulated upon activation, normal T cell expressed and secreted (RANTE S). Distributions of all three were positively skewed. CSF chemokine concen trations were correlated with each other and were higher in demented patien ts. In a multivariate analysis, demented subjects were more likely to have detectable CSF MIP-1 alpha, elevated CSF HIV RNA levels, and lower CD4(+) c ell counts. However, among those with detectable CSF MIP-1 alpha, levels we re lower in demented patients. CSF beta chemokine elevation is consistent w ith the macrophage activation known to occur in dementia and with studies o f beta chemokine mRNA expression in the brain. Low, but detectable, levels of CSF MIP-1 alpha were strongly associated with dementia, suggesting that higher levels may have neuroprotective effects.