Plasma cytokine concentrations associated with HIV/hepatitis C coinfection are related to attention, executive and psychomotor functioning

Abstract

Cytokine disturbances have been linked to brain dysfunction among HIV-infected people. Past studies have not simultaneously examined a large set of cytokine measures and their relationships to HIV-associated neurocognitive deficits. We hypothesized that performance on measures of attention and executive and psychomotor functions would be associated with plasma cytokine concentrations in HIV-infected individuals. Plasma samples drawn from 30 HIV-infected and 37 HIV seronegative individuals were analyzed via xMAP multiplexed bead array immunoassay to determine concentrations of 13 cytokines. Performance on Trail Making A/B, Stroop Test, Letter-Number Sequencing, Digit Symbol Coding, Symbol Search, and Grooved Pegboard tests was assessed. Statistical analyses were performed to examine group differences in cytokine concentrations, and associations between cytokine and HIV clinical variables and neurocognitive performance. Significant HIV effects were found on 7 of the 13 cytokines, primarily with respect to interleukins. HIV clinical factors (CD4 and HIV RNA levels, duration of illness, antiretroviral treatment) and hepatitis C status were associated with specific plasma cytokine concentrations. Neurocognitive measures were associated with cytokine concentrations, most consistently among the interleukins and IP-10. Generally, cytokine concentrations were among the strongest predictors of neurocognitive function relative to other clinical factors, which reinforces their potential importance in examining the neuropathological processes of HIV. The findings also point to the potential value of simultaneously examining a panel of biomarkers. The current results suggest that a complex relationship likely exists among cytokines [how?] and that these relationships are mediated not only by HIV infection but also by antiretroviral treatment and other comorbid conditions.