Pathways of neuro-immune communication: past and present time, clinical application

Abstract

Fundamental studies in neuroimmunophysiology are the keystone for development of new therapeutic approaches to the treatment of infectious, allergic, oncologic and autoimmune diseases. The achievements in this field allowed approving new treatment methods based on irritation of afferent and efferent fibers of autonomic nerves. That became possible due to numerous studies of pathways between the immune and nervous systems performed over last two decades. The milestones in the history of neuroimmune communication research are represented here. The immune system organs – bone marrow, thymus and spleen are coupled to central nervous system (CNS) via sympathetic nerves. Information about LPS and bacteria emergence in peritoneum, intestine and parenchymal organs reaches the brain via parasympathetic pathways. After vagotomy, the brain neurons do not respond to this kind of antigens. The pattern of brain responses to different applied antigens (the EEG changes and the quantity of c-Fos-positive neurons) is specific for definite antigen, like as algorithms of electroneurogram after exposure to different cytokines. Activation of parasympathetic nerves causes the inhibition of inflammation. The entry of any antigens into the body initiates production of cytokines (IL-1, TNFα, IL-6, IFNγ etc.), via specific receptors which are present on peripheral neurons and terminals of vagus nerve, i.e. the vagal afferent terminals and neurons respond to cytokine action, and these signals are transmitted to CNS neurons. The afferent vagal fibers end on the dorsal vagal complex neurons in the caudal part of medulla oblongata. The information about bacterial antigens, LPS and inflammation is transmitted to the brain via afferent autonomic neural pathways. The speed of this process is high and significantly depends on the rates of cytokine production that are transmitters of signals upon the antigen exposure. It is important to emphasize that this events occur within minutes, and the response to the received information proceeds by reflex mechanisms, i.e., within fraction of a second, as exemplified by inflammation (“inflammation reflex”). This is a fundamentally new and revolutionary discovery in the functional studies of immune system regulation. Clinical efficiency of n. vagus stimulation by pulsed ultrasound was shown, being used for the treatment of inflammatory, allergic and autoimmune diseases, e.g., multiple sclerosis, rheumatoid arthritis, renal inflammatory diseases. Electrical stimulation of the vagus nerve reduces the death of animals in septic shock by 80%. The mentioned data have made a revolution in understanding the functional arrangement of immune system in the body. A hypothesis is represented, which suggests how the information on the antigen exposure is transmitted to the brain.

Effects of transcutaneous electrical stimulation with the device “VEB” ® on the human body

“…The first part of the program for adjusting the level of the output signal lasts 20 seconds, after which the main part of the program (generation of pulse current of alternating frequency in the range from 144 Hz to 1120 Hz) lasts for 21 ("VEB-1") or 26 ("VEB-2") minutes. It is known about the functional relationships between EEG and HRV parameters [41,44,49] as well as neuroimmunomodulation [27,28,36,42,43,[45][46][47][48]. From here we hypothesized that changes in EEG parameters may be accompanied by a change in HRV and immune parameters.…”

Energetic therapy for psycho-emotional conditions in children and adolescents with vegetative dystonia

“…За последние 20-30 лет сформировалось новое самостоятельное научное направлениенейроиммуноэндокринология. Нейроиммуноэндокринные взаимодействия, выполняющие интегративные регулирующие функции, играют важнейшую роль в обеспечении целостности организма [7][8][9]. По данным Г.Н.…”

“…В последние годы установлены новые функции иммунной системы [8,9]. Иммуноциты, реагирующие на антигены, продуцируют нейропептиды и гормоны, идентичные гормонам гипофиза.…”

cFos Protein Synthesis in Medulla Oblongata after Intraperitoneal Injection of Staphylococcus Enterotoxin B (SEB) on the Background of Selective Subdiaphragmatic Vagotomy

“…Vagus sensory neurons express a wide range of receptors, including receptors for neuromodulators, cytokines, and growth factors [1,2]. In this regard, vagus nerve is a key pathway of information transmission from the immune system of the peritoneal and pleural cavities to the CNS [3]. The aim of this work was to determine the degree of activation of the cells in vagus nuclei NTX and DMX after administration of staphylococcus enterotoxin B (SEB) with and without selective subdiaphragmatic vagotomy (SSV).…”

“…An analysis of the complex data concerning the issue of information exchange pathways between the immune and nervous systems made it possible to propose a hypothesis about the fundamental mechanisms of information transmission along the nervous pathways [3]. The meaning of the hypothesis is that antigen action leads to producing a complex of cytokines by the cells of the immune system.…”