Stress-Associated Immune Modulation and Its Implications for Reactivation of Latent Herpesviruses

There is an extensive literature concerned with the integration of the immune system with the central nervous system (CNS) and endocrine systems. Each of these body systems is complex, and studying the interactions among the three systems raises the complexity by orders of magnitude. The field of “psychoneuroimmunology” or “neuroimmunomodulation” is a rapidly de veloping field and encompasses these interactions; it also includes the study of behavior as a modulator of the interaction. There is experimental evidence suggesting that the CNS/immune axis is bidirectional. The immune system receives signals from the CNS (e.g., neuropeptides) and from the endocrine system (e.g., glucocorticoids, prolactin, and growth hormone). Feedback from the immune system modulates the CNS-for example, the influence of interleukin-1 (IL-1) on the hypothalamus. More than likely, this feedback also includes other cytokines and growth factors made by lymphocytes themselves, such as the adrenocorticotropic hormone (ACTH) (1). It is clear that one needs to think about the historical roles of lymphokines, growth factors, hormones, and neuropeptides in an ex panded way to include a much broader biological responses.