ABSTRACT
BACKGROUND: Adults who undergo chronic stress, such as the diagnosis and surgical treatment of breast cancer, often experience adjustment difficulties and important biologic effects. This stress can affect the immune system, possibly reducing the ability of individuals with cancer to resist disease progression and metastatic spread. We examined whether stress influences cellular immune responses in patients following breast cancer diagnosis and surgery. METHODS: We studied 116 patients recently treated surgically for invasive breast cancer. Before beginning their adjuvant therapy, all subjects completed a validated questionnaire assessing the stress of being cancer patients. A 60-mL blood sample taken from each patient was subjected to a panel of natural killer (NK) cell and T-lymphocyte assays. We then developed multiple regression models to test the contribution of psychologic stress in predicting immune function. All regression equations controlled for variables that might exert short- or long-term effects on these responses, and we also ruled out other potentially confounding variables. RESULTS: We found, reproducibly between and within assays, the following: 1) Stress level significantly predicted lower NK cell lysis, 2) stress level significantly predicted diminished response of NK cells to recombinant interferon gamma, and 3) stress level significantly predicted decreased proliferative response of peripheral blood lymphocytes to plant lectins and to a monoclonal antibody directed against the T-cell receptor. CONCLUSIONS: The data show that the physiologic effects of stress inhibit cellular immune responses that are relevant to cancer prognosis, including NK cell toxicity and T-cell responses. Additional, longitudinal studies are needed to determine the duration of these effects, their health consequences, and their biologic and/or behavioral mechanisms.
Subject(s)
Breast Neoplasms/immunology , Breast Neoplasms/psychology , Stress, Psychological/immunology , Adult , Aged , Antineoplastic Agents/pharmacology , Breast Neoplasms/surgery , Female , Humans , Interferon-gamma/pharmacology , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Middle Aged , Predictive Value of Tests , Recombinant Proteins/pharmacology , Regression Analysis , Reproducibility of Results , T-Lymphocytes/drug effects , T-Lymphocytes/immunologyABSTRACT
Among the various factors thought to be associated with the reactivation of latent herpesviruses is psychological stress. An increase in levels of 'stress hormones' such as glucocorticoids occurs in individuals who are stressed and previous studies have shown that glucocorticoid hormones can reactivate latent Epstein-Barr virus (EBV) in vitro. In this study, we confirm that the EBV genome in latently infected lymphoblastoid cells can be reactivated with two glucocorticoid hormones, hydrocortisone and dexamethasone. In addition to hydrocortisone and dexamethasone, we also found that other hormones of the hypothalamic-pituitary-axis (corticotropin-releasing factor and adrenocorticotropin hormone but not epinephrine and norepinephrine) as well as somatostatin can enhance the lytic replication of the HR-1 strain of EBV in superinfected cells. These results suggest that multiple endocrine interactions may be involved in stress-induced reactivation/replication of latent EBV.
