Cytokines in CSF correlate with HIV-associated neurocognitive disorders in the post-HAART era in China

Abstract

In the current era of highly active antiretroviral therapy (HAART), the incidence of HIV dementia has declined, but the prevalence of HIV-associated neurocognitive disorder (HAND) remains high. HIV-induced systemic and localized inflammation is considered to be one of the mechanisms of HAND. Changes in cytokine levels in the cerebrospinal fluid (CSF) during HIV infection might help to identify HAND. To investigate whether the cytokine profile of the CSF during HIV infection could be used as a biomarker of HAND, we compared cytokine levels in the CSF of HIV-infected cases with and without neurocognitive impairment. Cytokine concentrations in the CSF were measured by quantification bioassays (Luminex xMAP). HIV-infected cases with neurocognitive impairment demonstrated higher levels of interleukin (IL)-8, monocyte chemotactic protein (MCP)-1, induced protein (IP)-10, and granulocyte colony-stimulating factor (G-CSF) in the CSF than those without neurocognitive impairment (G-CSF (p = 0.0003), IL-8 (p = 0.0046), IP-10 (p < 0.0001), and MCP-1 (p < 0.0001)). There was no significant impact of HAART on cytokine levels in the CSF, except for IP-10, which was higher in HAART-treated patients with impaired cognition (p = 0.0182). Findings from this preliminary study suggest that elevated levels of the cytokines IL-8, MCP-1, G-CSF, and IP-10 in the CSF are associated with neurocognitive impairment in HIV infection, and these cytokines likely represent a biomarker profile for HAND.

Fig. 1

Comparison of G-CSF, IL-8, IP-10, and MCP-1 concentrations in the CSF in samples from 64 HIV-infected subjects with impaired cognition (HIV-CI) and 43 HIV-infected subjects with normal cognition (HIV-NC). Values below the lower limit of detection of the assay are reported as zero (a). HIV RNA levels in the CSF were also compared (b). The levels of G-CSF, IL-8, IP-10, and MCP-1 in the CSF in the HIV-CI group were significantly higher than in the HIV-NC group, whereas no difference was found in the HIV RNA levels in the CSF. Differences were analyzed by the Mann–Whitney U test. p values of <0.05 were considered significant. Dots cytokine or RNA level in the CSF for each study subject, horizontal lines median values for each group

Fig. 2

The concentrations of G-CSF, IL-8, IP-10, and MCP-1 in the CSF were compared between HAART-treated and untreated patients in the HIV-CI group and HIV-NC group. There was no significant difference, except for IP-10, which was higher in HAART-treated patients than in untreated patients within the HIV-CI group (p=0.0182; a). HIV RNA levels in the CSF and plasma were lower in HAART-treated patients than in untreated patients (b), whereas CD4+ cells showed no difference between the two groups (c). The differences between groups were calculated using the Mann–Whitney U test. P values of <0.05 were considered significant. Dots cytokine level, viral load or CD4+ cell count for each study subject; horizontal lines median values for each group