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Sympathoimmune Anomalies Underlying the Response to Stressful Challenge in Human Immunodeficiency Virus Spectrum Disease

From the Behavioral Medicine Research Center (B.E.H., K.A.B., S.J.M., J.R.M., J.L.K., L.F., W.G.L., N.S.), Department of Psychology (B.E.H., K.A.B., S.J.M., J.R.M., J.L.K., L.F., N.S.), Department of Biomedical Engineering (B.E.H.), University of Miami, Miami, Florida; Division of Endocrinology and Metabolism (B.E.H., N.S.), Department of Psychiatry (M.K., N.S.), Department of Immunology and Microbiology (N.G.K., M.A.F.), School of Medicine, University of Miami, Miami, Florida.

Address correspondence and reprint requests to Barry E. Hurwitz, PhD, Behavioral Medicine Research Center (200 BMRC), University of Miami, c/o VA Medical Center, 1201 NW 16th Street, Miami, FL 33125. E-mail bhurwitz{at}miami.edu

Objective: This study examined immune, endocrine, and cardiovascular reactivity during stressful behavioral challenge in human immunodeficiency virus (HIV) seropositive (HIV+) and seronegative (HIV–) men and women and assessed whether immunocellular reactivity was differentially associated with concomitant alterations in sympathetic response.

Methods: The 133 HIV+ [84 asymptomatic, 49 symptomatic] and 92 HIV– subjects completed a speech stress reactivity protocol.

Results: Immunocellular reactivity to the speech stressor did not differ among asymptomatic and symptomatic HIV+ groups; however, relative to seronegatives, reactivity differences were present. Specifically, HIV+ subjects exhibited greater increases in total number of T cells, as well as in cytotoxic/suppressor T cells, activated T cells, and activated cytotoxic/suppressor T cells, and less increase in natural killer (NK) cell numbers. In addition, less stress-induced increase in NK cell cytotoxicity was observed along with greater suppression of the lymphoproliferative response to mitogen stimulation in the HIV+ group. Although no group differences in catecholamine reactivity were observed, the association of immunoreactivity with catecholamine responsiveness differed between serostatus groups. Specifically, the HIV+ subjects compared with HIV– subjects displayed greater lymphocytosis per unit change in norepinephrine; whereas NK cell reactivity was positively related to epinephrine responsiveness, but only in the HIV– group. These findings were present even after controlling for age and body mass, as well as other potential influences on immunocellular migration, such as cortisol levels and prevailing cardiac output.

Conclusion: Early in HIV spectrum disease, functional abnormalities in the stress-induced migratory ability of specific immunocellular subsets are present that may reflect an underlying pathophysiological alteration in sympathoimmune communication.

Key Words: HIV • stress • cardiovascular • immune • catecholamines • sympathetic

Abbreviations: ACTH = adrenocorticotropin hormone; AIDS = acquired immunodeficiency syndrome; BMI = body mass index; C/S T cell = cytotoxic/suppressor T cell; cAMP-PKA = cyclic adenosine monophosphate-dependent protein kinase; CD38 = activation marker; CV = coefficient of variation; DBP = diastolic blood pressure; ECG = electrocardiogram; EPI = epinephrine; HIV = human immunodeficiency virus; HIV– = HIV seronegative; HIV+ = HIV seropositive; HIV+ A = HIV seropositive asymptomatic; HIV+ S = HIV seropositive symptomatic; HLA/DR = activation marker; ICG = impedance cardiogram; LPR = lymphocyte proliferation response; NE = norepinephrine; NK = natural killer; NKCC = natural killer cell cytotoxicity; PCG = phonocardiogram; PHA = phytohemagglutinin mitogen; SBP = systolic blood pressure; TPR = total peripheral resistance; = delta or change score.

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