Chemokines in cerebrospinal fluid correlate with cerebral metabolite patterns in HIV-infected individuals

Scott L. Letendre, Jialin C. Zheng, Marcus Kaul, Constantin T. Yiannoutsos, Ronald J. Ellis, Michael J. Taylor, Jennifer Marquie-Beck, Bradford Navia

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Chemokines influence HIV neuropathogenesis by affecting the HIV life cycle, trafficking of macrophages into the nervous system, glial activation, and neuronal signaling and repair processes; however, knowledge of their relationship to in vivo measures of cerebral injury is limited. The primary objective of this study was to determine the relationship between a panel of chemokines in cerebrospinal fluid (CSF) and cerebral metabolites measured by proton magnetic resonance spectroscopy (MRS) in a cohort of HIV-infected individuals. One hundred seventy-one stored CSF specimens were assayed from HIV-infected individuals who were enrolled in two ACTG studies that evaluated the relationship between neuropsychological performance and cerebral metabolites. Concentrations of six chemokines (fractalkine, IL-8, IP-10, MCP-1, MIP-1β, and SDF-1) were measured and compared with cerebral metabolites individually and as composite neuronal, basal ganglia, and inflammatory patterns. IP-10 and MCP-1 were the chemokines most strongly associated with individual cerebral metabolites. Specifically, (1) higher IP-10 levels correlated with lower N-acetyl aspartate (NAA)/creatine (Cr) ratios in the frontal white matter and higher MI/Cr ratios in all three brain regions considered and (2) higher MCP-1 levels correlated with lower NAA/Cr ratios in frontal white matter and the parietal cortex. IP-10, MCP-1, and IL-8 had the strongest associations with patterns of cerebral metabolites. In particular, higher levels of IP-10 correlated with lower neuronal pattern scores and higher basal ganglia and inflammatory pattern scores, the same pattern which has been associated with HIV-associated neurocognitive disorders (HAND). Subgroup analysis indicated that the effects of IP-10 and IL-8 were influenced by effective antiretroviral therapy and that memantine treatment may mitigate the neuronal effects of IP-10. This study supports the role of chemokines in HAND and the validity of MRS as an assessment tool. In particular, the findings identify relationships between the immune response - particularly an interferon-inducible chemokine, IP-10 - and cerebral metabolites and suggest that antiretroviral therapy and memantine modify the impact of the immune response on neurons.

Original languageEnglish (US)
Pages (from-to)63-69
Number of pages7
JournalJournal of neurovirology
Volume17
Issue number1
DOIs
StatePublished - Feb 2011

Keywords

  • Brain
  • CSF
  • Chemokines
  • HIV
  • Magnetic resonance spectroscopy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

Fingerprint Dive into the research topics of 'Chemokines in cerebrospinal fluid correlate with cerebral metabolite patterns in HIV-infected individuals'. Together they form a unique fingerprint.

Cite this