BACKGROUND: Products of immune activation, including cytokines and lipid membrane derivatives, have been implicated in the pathogenesis of the neurologic sequelae, including autonomic dysfunction, associated with human immunodeficiency virus 1 (HIV-1) infection. In animal models, autonomic and endocrine dysfunction are associated with an altered cytokine profile. OBJECTIVES: To investigate the relationship between markers of immune activation (beta(2)-microglobulin), HIV-1 disease progression (CD4(+) cell count and viral load), and autonomic nervous system performance and to assess the relationship between autonomic performance, plasma levels of dehydroepiandrosterone sulfate (DHEAS), and T(H)1 and T(H)2 cytokine profile. METHODS: Thirty-one HIV-1-infected individuals and 22 HIV-1-negative controls were evaluated with a comprehensive neurologic, neuropsychological, and autonomic examination. Interleukin 4 and interferon gamma were measured by enzyme-linked immunosorbent assay in the supernatant of stimulated peripheral blood mononuclear cells. RESULTS: A composite measure of autonomic performance (AZ score) was significantly 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 significantly inversely associated with AZ score (P=.01), whereas interferon gamma levels were significantly positively associated with DHEAS levels (P=.04). CONCLUSIONS: Our data show significant associations between markers of immune 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.
BACKGROUND: Products of immune activation, including cytokines and lipid membrane derivatives, have been implicated in the pathogenesis of the neurologic sequelae, including autonomic dysfunction, associated with human immunodeficiency virus 1 (HIV-1) infection. In animal models, autonomic and endocrine dysfunction are associated with an altered cytokine profile. OBJECTIVES: To investigate the relationship between markers of immune activation (beta(2)-microglobulin), HIV-1 disease progression (CD4(+) cell count and viral load), and autonomic nervous system performance and to assess the relationship between autonomic performance, plasma levels of dehydroepiandrosterone sulfate (DHEAS), and T(H)1 and T(H)2 cytokine profile. METHODS: Thirty-one HIV-1-infected individuals and 22 HIV-1-negative controls were evaluated with a comprehensive neurologic, neuropsychological, and autonomic examination. Interleukin 4 and interferon gamma were measured by enzyme-linked immunosorbent assay in the supernatant of stimulated peripheral blood mononuclear cells. RESULTS: A composite measure of autonomic performance (AZ score) was significantly 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 significantly inversely associated with AZ score (P=.01), whereas interferon gamma levels were significantly positively associated with DHEAS levels (P=.04). CONCLUSIONS: Our data show significant associations between markers of immune 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.
Authors: Edward L Nelson; Lari B Wenzel; Kathryn Osann; Aysun Dogan-Ates; Nissa Chantana; Astrid Reina-Patton; Amanda K Laust; Kevin P Nishimoto; Alexandra Chicz-DeMet; Nefertiti du Pont; Bradley J Monk Journal: Clin Cancer Res Date: 2008-04-01 Impact factor: 12.531