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

• Published in: Journal of neurovirology Vol. 17; no. 1; pp. 63 - 69
• Main Authors: Letendre, Scott L., Zheng, Jialin C., Kaul, Marcus, Yiannoutsos, Constantin T., Ellis, Ronald J., Taylor, Michael J., Marquie-Beck, Jennifer, Navia, Bradford
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.02.2011
• Subjects: Adult; Aspartic Acid - analogs & derivatives; Aspartic Acid - analysis; Biomedical and Life Sciences; Biomedicine; CD4 Lymphocyte Count; Cerebrum - metabolism; Cerebrum - virology; Chemokines - cerebrospinal fluid; Cohort Studies; Creatine - analysis; Female; HIV - pathogenicity; HIV Infections - cerebrospinal fluid; Human immunodeficiency virus; Humans; Immunology; Infectious Diseases; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neurology; Neurosciences; Virology; Magnetic resonance spectroscopy; Brain; HIV; Chemokines; CSF
• ISSN: 1355-0284; 1538-2443
• DOI: 10.1007/s13365-010-0013-2

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.