Neuroendocrineimmunology (NEI) at the turn of the century: Towards a molecular understanding of basic mechanisms and implications for reproductive physiopathology

The interactions between the nervous, endocrine and immune systems require a complex communication network. The central nervous system (CNS) affects the immune system through endocrine, paracrine and neuronal mechanisms. Evidence that this bidirectional communication plays a vital role in the regulation of physiological homeostatic mechanisms while a disfunction of the neuroendocrineimmune balance favors the susceptibility to a number of diseases is derived largely by animal models but also by an increasing number of clinical studies in different fields, including endocrinology, reproductive physiology, pediatrics, oncology, neurology and psychiatry. An increasing number of endocrine hormones, neurotransmitters and neuropeptides are expressed in immune tissues and cells and are actively involved in the physiological regulation of immunity. Conversely, the endocrine and nervous systems harbor receptors for a wide variety of immunologically-derived substances, suggesting potential regulatory feedback loops between the three major integrative bodily systems. Major implications for the reproductive endocrinology field are that psychoneuroendocrine processes may alter fertility via immunomodulation, and that events that occur as part of immune responses influence the neuroendocrine axes, which in turn counter-regulate immune function. In the present article, some features of reproductive-immune interactions will be described, and the neuroendocrineimmune dialogue via the chief reproductive hormone, luteinizing hormone-releasing hormone (LHRH), will be summarized as prototype of intersystem crosstalk. A particular emphasis will be given to the cytokine-LHRH interrelationships both at central (i.e. especially with the astroglial compartment) and peripheral levels. The surprisingly similar communication network systems used by the gonads and the thymus will be summarized, and the sexually-driven dimorphisms dictating female versus male reproductive and immunological capacities reviewed. Evidence that neural, endocrine and immune systems work together as a single unit are emphasized in animal models and human pathologies where interruption of NEI feedback loops results in long lasting pathological consequences for the nervous, endocrine and immune functions.