mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-PON-1974mimmun-1974Research ArticleОБЗОРЫREVIEWSПути взаимодействия нервной и иммунной систем: история и современность, клиническое применениеPathways of neuro-immune communication: past and present time, clinical applicationhttps://orcid.org/0000-0002-4999-5913КорневаЕ. А.KornevaE. A.

Корнева Елена Андреевна – д.м.н., профессор, академик РАН, главный научный сотрудник отдела общей патологии и патологической физиологии

197376, Санкт-Петербург, ул. Акад. Павлова, 12.Тел.: 8 (812) 234-07-24.

Korneva Elena A. – PhD, MD (Medicine), Professor, Full Member, Russian Academy of Sciences, Chief Research Associate, Department of General Pathology and Pathophysiology

197376, St. Petersburg, Acad. Pavlov str., 12.Phone: 7 (812) 234-07-24.

korneva_helen@mail.ruФГБНУ «Институт экспериментальной медицины»РоссияInstitute of Experimental MedicineRussian Federation202020052020223405418Copyright © Корнева Е.А., 20202020Корнева Е.А.Korneva E.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/1974

Фундаментальные исследования в области нейроиммунофизиологии являются основой для разработки новых способов терапии инфекционных, аллергических, опухолевых и аутоаллергических заболеваний. Успехи, достигнутые в этой области, позволили обосновать и предложить новые способы лечения заболеваний аутоиммунной природы, влияя на механизмы реализации нейроиммунного взаимодействия, в частности на афферентные и эфферентные волокна вегетативных нервов. Это стало возможным в результате исследований путей обмена информации между нервной и иммунной системами, которые были выполнены в последнее двадцатилетие. Представлены основные вехи истории изучения путей реализации взаимодействия нервной и иммунной систем. Органы иммунной системы – костный мозг, тимус, селезенка – связаны с ЦНС через симпатические нервы. Информация о поступлении бактериальных антигенов и LPS в брюшную полость, кишечник и паренхиматозные органы поступает в мозг по парасимпатическим путям, и при перерезке n. vagus нейроны ЦНС не реагируют на их введение. Электрофизиологические исследования и анализ в структурах гипоталамуса количества клеток, содержащих c-Fos белок – маркер активации нейронов – свидетельствуют о том, что паттерн активации структур мозга при введении различных антигенов различен. Существенно подчеркнуть, что алгоритм изменений электронейрограммы характерен для реакции на определенный цитокин. Поступление любых антигенов в организм инициирует продукцию цитокинов (IL-1, TNF, IL-6, IFNγ и др.), рецепторы к которым представлены на периферических нейронах и нервных окончаниях вагуса, то есть афферентные окончания и нейроны вагуса могут отвечать на действие цитокинов, и эти сигналы передаются в нейроны центральной нервной системы. Афферентные волокна вагуса оканчиваются в нейронах дорзального комплекса вагуса в каудальной части продолговатого мозга. Информация о поступлении бактериальных антигенов, LPS и воспалении поступает в мозг по афферентным вегетативным нервным путям, скорость этого процесса велика и во многом зависит от скорости продукции цитокинов как передатчиков сигналов об антигенном воздействии. Комплекс представленных в литературе и собственных данных позволяет сформулировать гипотезу организации процесса передачи информации от иммунной системы в мозг по вегетативным нервам. Важно подчеркнуть, что этот процесс происходит в течение минут, а ответ на поступившую информацию реализуется по механизмам рефлекса, то есть в течение долей секунд, что показано при воспалении («рефлекс воспаления»). Это принципиально новое и революционное открытие в изучении регуляции функций иммунной системы. Активация парасимпатической нервной системы ведет к снижению воспалительных процессов. Электрическая стимуляция вагуса снижает гибель животных при септическом шоке на 80%. Показана эффективность раздражения n. vagus пульсирующим ультразвуком в клинике при лечении заболеваний воспалительной, аллергической и аутоаллергической природы.

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.

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The authors declare that there are no conflicts of interest present.