Journal of NeuroVirology

, Volume 17, Issue 1, pp 63-69

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • Scott L. LetendreAffiliated withUniversity of California, San Diego Email author 
  • , Jialin C. ZhengAffiliated withUniversity of Nebraska Medical Center
  • , Marcus KaulAffiliated withThe Sanford-Burnham Institute
  • , Constantin T. YiannoutsosAffiliated withIndiana University School of Medicine
  • , Ronald J. EllisAffiliated withUniversity of California, San Diego
  • , Michael J. TaylorAffiliated withUniversity of California, San Diego
  • , Jennifer Marquie-BeckAffiliated withUniversity of California, San Diego
  • , Bradford NaviaAffiliated withTufts Medical School
  • , for the HIV Neuroimaging Consortium


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.


CSF Chemokines Magnetic resonance spectroscopy HIV Brain