Neuroendocrine Effects On Anti-Viral Immunity

There is substantial experimental evidence indicating that the immune system is functionally integrated with both the central nervous system and endocrine system. Recent studies in both humans and in animals suggest that this neuroendocrine-immune axis operates bi-directionally in that the immune system receives and responds to signals originating from the nervous and endocrine systems as well as delivering signals to which these systems can each respond. This intercellular communication is mediated through receptor-specific binding of lymphokines, hormones, and neuropeptides as well as by direct contact between nerve fibers and cells of the immune system within the architecture of immune tissues such as the thymus, lymph nodes, and spleen. As a result, immune responses are potentially subject to direct neuroendocrine regulation. In addition, a number of studies have demonstrated that psychologically stressful events play a significant role in modulation of both humoral and cellular immunity through such neuroendocrine-immune interactions. However, few studies have focused on elucidating the mechanisms that underlie stress-induced modulation of the immune response that is necessary for resolution of a specific virus infection. The overall aim of our research is to use an established murine model system of herpes simplex virus (HSV) infection to investigate the mechanisms underlying stress-associated neuroendocrine interactions with the immune system and how these interactions may contribute to the pathogenesis of HSV infection. These studies focus on the stress-associated activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system and their role in modulating the activation and function of both primary and memory HSV-specific cytotoxic T lymphocytes (CTL). Overall, these studies will provide insight into the role of and mechanisms by which stress-related neuroendocrine activation modulate anti-viral immune responses and should contribute significantly to the overall understanding of the relationship among neuroendocrine-associated alterations in immune function and viral pathogenesis.