The Psycho-Neuro-Endocrino-Immunology (Pnei) of the Cardiovascular System

The immune system has appeared to regulate not only the immune response, but all biological functions, including the nervous, the endocrine and the cardiovascular systems. At the other side, the immune system is under a physiological psycho neuroendocrine regulation, mainly modulated by the pineal gland and the opioid system, respectively in a stimulatory or in a suppressive way by influencing the cytokine network. The different cytokines exert different immunobiological effects on the immune cells, mainly by influencing the interactions between lymphocyte and monocyte-macrophage systems. The functionless of the whole immune system may be synthesized by the lymphocyte-to-monocyte ratio (LMR), and the evidence of an abnormally low LMR has been proven to be associated with a poor prognosis in all systemic severe inflammation-related human diseases, including cancer, autoimmune diseases and the cardiovascular disorders. Within the cytokine group, lL-17, IL-6, IL-1 beta, TNF alpha, and IL-18 represent the most important inflammatory cytokines involved in systemic human pathologies, whereas the most effective anti-inflammatory cytokines are consisting of TGF-beta and IL-10. The evidence of abnormally high levels of inflammatory cytokines may predict a worse prognosis in all systemic diseases. Within the neuroendocrine system, the secretion of melatonin (MLT), which represents the most investigated immunomodulating pineal hormone, has appeared to increase LMR by stimulating lymphocyte proliferation and inhibiting the monocyte macrophage system. Moreover, it has been shown that a decrease in MLT secretion may be associated with a poor prognosis in cardiovascular diseases. Therefore, MLT administration could be effective in reducing myocardial infarction and stroke-induced tissue damage. Further studies, by concomitantly evaluating MLT secretion in relation to changes in LMR values, as well as in IL-17 and IL-18 blood levels, will be required to establish whether the immune changes occurring during cardiovascular and systemic inflammatory diseases may depend at least in part on a diminished pineal function.