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Relationship to T_H1 and T_H2 Cytokine Profile

Giovanni Schifitto, MD; Michael P. McDermott, PhD; Thomas Evans, MD; Theresa Fitzgerald, BSc; Joshua Schwimmer, MD; Lisa Demeter, MD; Karl Kieburtz, MD, MPH

Arch Neurol. 2000;57:1027-1032.

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 (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_H1 and T_H2 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 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.

From the Departments of Neurology (Drs Schifitto, McDermott, and Kieburtz), Biostatistics (Dr McDermott), and Medicine (Drs Evans, Schwimmer, and Demeter and Ms Fitzgerald), University of Rochester, Rochester, NY.

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