Chemokines in cerebrospinal fluid correlate with cerebral metabolite patterns in HIV-infected individuals.
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.
University of California, San Diego, 220 Dickinson Street, Suite A, San Diego, CA 92103, USA. sletendre@ucsd.edu
Scott L
SL
Letendre
Jialin C
JC
Zheng
Marcus
M
Kaul
Constantin T
CT
Yiannoutsos
Ronald J
RJ
Ellis
Michael J
MJ
Taylor
Jennifer
J
Marquie-Beck
Bradford
B
Navia
D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D018791:CD4 Lymphocyte Count; D054022:Cerebrum / Q000378:metabolism* / Q000821:virology; D018925:Chemokines / Q000134:cerebrospinal fluid*; D015331:Cohort Studies; D003401:Creatine / Q000032:analysis; D005260:Female; D006678:HIV / Q000472:pathogenicity*; D015658:HIV Infections / Q000134:cerebrospinal fluid*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged
D018925:Chemokines; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine
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