Autonomic performance and dehydroepiandrosterone sulfate levels in HIV-1-infected individuals - Relationship to T(H)1 and T(H)2 cytokine profile

Background: Products of immune activation, including cytokines and lipid me mbrane derivatives, have been implicated in the pathogenesis of the neurolo gic sequelae, including autonomic dysfunction, associated with human immuno deficiency virus 1 (HIV-1) infection. In animal models, autonomic and endoc rine dysfunction are associated with an altered cytokine profile. Objectives: To investigate the relationship between markers of immune activ ation (beta(2)-microglobulin), HIV-1 disease progression (CD4(+) cell count and viral load), and autonomic nervous system performance and to assess th e relationship between autonomic performance, plasma levels of dehydroepian drosterone sulfate (DHEAS), and T(H)1 and T(H)2 cytokine profile. Methods: Thirty-one HIV-l-infected individuals and 22 HIV-1-negative contro ls were evaluated with a comprehensive neurologic, neuropsychological, and autonomic examination. Interleukin 4 and interferon gamma were measured by enzyme-linked immunosorbent as-say in the supernatant of stimulated periphe ral blood mononuclear cells. Results: A composite measure of autonomic performance (AZ score) was signif icantly lower (worse autonomic function) in patients compared with controls (P=.04). A lower AZ score was associated with higher beta(2)-microglobulin serum levels and a lower CD4(+) cell count. Interleukin 4 levels were sign ificantly inversely associated with AZ score (P=.01), whereas interferon ga mma levels were significantly positively associated with DHEAS levels (P=.0 4). Conclusions: Our data show significant associations between markers of immu ne activation and disease progression and a composite measure of autonomic function in HIV-1-infected individuals. In addition, they suggest that poor autonomic function and low DHEAS plasma levels tend to be associated with an unbalanced cytokine profile.