There is a strong popular belief in midbody interaction since prehistoric times. Pathologists noted first that the size of the thymus was profoundly influenced by emotional events and by neuroendocrine abnormalities. Hans Selye discovered (1936) that the hypothalamus-pituitary-adrenal axis was activated by diverse "nocuous" stimuli, which lead to a rapid involution of the thymus. He called the agents eliciting this phenomenon "stress". Selye concluded that stress induced a "general adaptation syndrome", which elevated the resistance of the animal to diverse insult. Hypothalamic lesions were shown to prevent anaphylactic death in guinea pigs in 1949 by Szentivanyi and colleagues. This demonstrated the dominant regulatory power of the nervous system over immune reactions. Korneva and Kai (1965) made similar observations were made in various animal species. Jancso and co-workers (1964) discovered the neural regulation of inflammation. These fundamental discoveries were not followed by intensive research activity. Progress has been slow because of the lack of basic knowledge and because of the immense technical difficulties encountered by investigators of this area.
In the seventies a handful of laboratories started to re-examine various aspects of neuroimmune-interaction. It was established that pituitary hormones have the capacity to stimulate, inhibit and modulate immune responses. Placental and pituitary hormones were also shown to be involved in immune system development and in the maintenance of immunocompetence (Berczi et al.). The innervation of lymphoid organs and cells was demonstrated. Neurotransmitters and neuropeptides were shown to be important immunomodulators. (Felten et al., Bienenstock et al.) Gradually immune derived cytokines were shown to deliver feedback signals towards the neuroendocrine system (Wenmacher, Besedovsky et al., Goldstein et al.). Compelling evidence was produced, indicating that immune reactions may be conditioned in the classical pavlovian sense and that emotions affect immune function (Ader et al., Bienenstock et al.). Evidence is increasing rapidly for the physiological role of cytokines and of immunocytes in the function of various organs and tissues, and in reproduction. It is also becoming obvious that Selye´s general adaptation syndrome corresponds to the acute phase response. This is a multi-faceted and highly coordinated systemic defence reaction, which involves the conversion of the immune system from a specific, adaptive mode of reactivity to a rapidly amplifiable polyspecific reaction mediated by natural immune mechanisms. Immunological (poly)specificity is assured by profoundly elevated levels of natural antibodies and liver-derived acute phase proteins.
Much has been learned about the regulation of cell activation, growth and function from immunological studies. Burnet´s clonal selectional theory designates antigen as the sole immune activator. Bretcher and Cohn recognized first that at least 2 signals are required. This was followed by numerous studies on cell-to-cell interaction within the immune system and led to our current understanding of the importance of cell adhesion molecules and cytokines in cell activation and proliferation. This, coupled with the available information about the mechanisms of action of hormones and neurotransmitters, and of signal transduction and nuclear regulatory pathways paves the way to understanding how higher organisms function in their entire complexity. It is now apparent that the Nervous- Endocrine- and Immune-systems form a systemic regulatory network, which is capable of regulating all aspects of bodily functions in health and disease. This provides new foundations for Biology.
The work was submitted to international scientific conference «Basic and applied research in medicine», Nov. 26 - Dec. 4, 2008 China (Beijing), came to the editorial office 08.08.2008.