A New Direction: Neuro-endocrino-immunology

Abstract

One of the unexpected and highly important biological discoveries of the last decade was that the psycho-neuroendocrine and the immune systems are not only in interaction, but also use common biochemical signals. The decoding of this common “language” was made possible with the help of the latest results of molecular biology and genetics. Not all details of this complex interaction are known today, but our current knowledge is satisfactory to state that it is not a separated, but an integrated psycho-neuroendocrino-mmune system that is responsible for the maintenance of the homeostasis in the body. Loss of this delicate balance may lead to various pathological conditions, thus to development of autoimmune diseases. It is known that the immune system is composed of a complicated network of cells with controlled interactions. The recognition of antigens is performed by monocytes, macrophages and dendritic cells (DC). This recognition is a complex process, consisting of the degradation of the substances taken up by the cells, the evaluation of the epitopes of the degraded substances, and transmission of the information gathered from these substances. The molecules of the so-called major histocompatibility complexes (MHC) have an important function in the recognition and presentation of antigens. The recognized information is transmitted to the thymus- and bursadependent cells (T and B lymphocytes). The former ones can also be divided into two groups. The Th1 (T helper 1) cells are responsible for the delayed type immune reactions, the Th2 (T helper 2) cells regulate the humoral immunological processes. T cells divide in the presence of activating agents (mitogenes) and antigens; they undergo the so-called blast transformation. During this process, they produce biologically active substances, part of which may be cytotoxic. B lymphocytes take effect via structurally and functionally different antibodies. Part of the antibodies bind to their own individual immunoglobulins (idiotype) and create the so-called idiotype–anti-idiotype network, which has an important role in the fundamental task of the immune system to preserve individual integrity. Other antibodies are cytotoxic or capable of inhibiting or stimulating the function of cells (e.g., anti-TSH receptor stimulating autoantibodies increasing thyroid function, or inhibitory autoantibodies in patients with Graves’ disease). Lymphokines produced by these cells were thought to be responsible for the interactions of the immune system. However, it has been recognized in the recent years that lymphokines are produced not only by the cells of the immune system, but by other cells, such as cells of the neuroendocrine system as well, therefore, nowadays these information transferring substances are rather called cytokines. Cytokines are polypeptide-type molecules binding specifically to cell surface proteins (receptors) and alter their function. The structure of cytokines and cytokine receptors is already known, some of them have also been successfully cloned. In contrast to hormones, cytokines deliver their effects dominantly in a paracrine or an autocrine fashion. However, it also has to be mentioned that sometimes there are overlaps between the effects of hormones and cytokines. This means that cytokines can be detected in the peripheral circulation, and they may act as hormones (e.g., interleukin-6 stimulates the hypothalamic–pituitary axis the most intensively), on the other hand, some hormones (e.g., prolactin, ACTH, TSH) are known to act as cytokines in the tissues (Fig. 4.1). Cytokines bind to specific receptors and may transmit inhibitory or stimulating signals. Cytokine receptors may detach from the surface of the cells and be present in a soluble form. These soluble cytokine receptors may be important partly in the regulation of cytokine production and partly in the effect of cytokines as well. Cytokine agonists and antagonist take effect in a different way, and they are expected to gain increasing therapeutic importance in the future. The basis of the holistic view of medicine is that it studies the physiological and pathological regulatory operations of the body in a unified way. The decoding of the integrative language summarizing the regulation of the human body has opened a new direction in medicine. The essence of this interaction is that the cells of the neuroendocrine system are capable to produce cytokines, while lymphocytes and macrophages produce neurotransmitters and hormones. The most recent results show that certain areas of the brain differentially coordinate the maturation and function of immune cells, and the “humunculus” model based on this indicates which brain regions regulate the maturation and activity of the immune system (Fig. 4.2).