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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Russian Journal of Immunology</journal-id><journal-title-group><journal-title xml:lang="en">Russian Journal of Immunology</journal-title><trans-title-group xml:lang="ru"><trans-title>Российский иммунологический журнал</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1028-7221</issn><issn publication-format="electronic">2782-7291</issn><publisher><publisher-name xml:lang="en">Russian Society of Immunology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">17074</article-id><article-id pub-id-type="doi">10.46235/1028-7221-17074-TTI</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>REVIEWS</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОБЗОРЫ</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">The issues of the neuro-immuno-endocrine system theory</article-title><trans-title-group xml:lang="ru"><trans-title>К вопросу теории нейроиммуноэндокринной системы</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Chereshnev</surname><given-names>Valeriy A.</given-names></name><name xml:lang="ru"><surname>Черешнев</surname><given-names>Валерий Александрович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>PhD, MD (Medicine), Professor, Full Member, Russian Academy of Sciences, Director for Research</p></bio><bio xml:lang="ru"><p>д.м.н., профессор, академик РАН, научный руководитель</p></bio><email>secretar@iip.uran.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Yushkov</surname><given-names>Boris G.</given-names></name><name xml:lang="ru"><surname>Юшков</surname><given-names>Борис Германович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>PhD, MD (Medicine), Professor, Corresponding Member, Russian Academy of Sciences, Chief Researcher, Laboratory of Immunophysiology and Immunopharmacology, Institute of Immunology and Physiology, Ural Branch, Russian Academy of Sciences; Head, Central Experimental Laboratory of Biotechnology, Institute of Medical Cellular Technologies</p></bio><bio xml:lang="ru"><p>д.м.н., профессор, член-корр. РАН, главный научный сотрудник лаборатории иммунофизиологии и иммунофармакологии ФГБУН «Институт иммунологии и физиологии» Уральского отделения Российской академии наук; заведующий Центральной экспериментальной лабораторией биотехнологий ГАУЗ СО «Институт медицинских клеточных технологий»</p></bio><email>b.yushkov@iip.uran.ru</email><xref ref-type="aff" rid="aff2"/><xref ref-type="aff" rid="aff3"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Institute of Medical Cellular Technologies, Yekaterinburg, Russia</institution></aff><aff><institution xml:lang="ru">ФГБУН «Институт иммунологии и физиологии» Уральского отделения Российской академии наук, г. Екатеринбург, Россия</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, Yekaterinburg, Russia</institution></aff><aff><institution xml:lang="ru">ФГБУН «Институт иммунологии и физиологии» Уральского отделения Российской академии наук, г. Екатеринбург, Россия</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">Institute of Medical Cellular Technologies, Yekaterinburg, Russia</institution></aff><aff><institution xml:lang="ru">ГАУЗ СО «Институт медицинских клеточных технологий», г. Екатеринбург, Россия</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2025-07-30" publication-format="electronic"><day>30</day><month>07</month><year>2025</year></pub-date><pub-date date-type="pub" iso-8601-date="2026-01-18" publication-format="electronic"><day>18</day><month>01</month><year>2026</year></pub-date><volume>29</volume><issue>1</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>9</fpage><lpage>34</lpage><history><date date-type="received" iso-8601-date="2024-09-30"><day>30</day><month>09</month><year>2024</year></date><date date-type="accepted" iso-8601-date="2025-07-24"><day>24</day><month>07</month><year>2025</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2026, Chereshnev V.A., Yushkov B.G.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2026, Черешнев В.А., Юшков Б.Г.</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="en">Chereshnev V.A., Yushkov B.G.</copyright-holder><copyright-holder xml:lang="ru">Черешнев В.А., Юшков Б.Г.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://rusimmun.ru/jour/article/view/17074">https://rusimmun.ru/jour/article/view/17074</self-uri><abstract xml:lang="en"><p>The review concerns the history of the evolution of views on the interrelations between the immune, nervous, and endocrine systems. The article presents arguments justifying the concept that they are components of a single regulatory system, since their structures are tightly integrated into each other and they use the same biologically active substances as signaling molecules. At the same time, the similar molecules may be categorized as either neurotransmitters, hormones, or cytokines, depending on the producing cells. E.g., the cytokine receptors have been found on peripheral neurons and vagal nerve endings, and IL-4 regulates synaptic transmission. The function of immune system cells to produce hormones and neuropeptides has been proven. Catecholamines may originate from cells of the immune system. Hypothalamic neurosecretory cells express IL-1, and astrocytic glial cells express interferon. In the functional regulation, they always act together, complementing or replacing each other, having a common coordinating center. Thus, the anterior lobe of pituitary gland, by producing growth hormone, affects the synthesis and secretion of thymulin by epithelial thymic cells. Hence, the hypothalamic-pituitary-thymic axis is formed. Neuroimmunoendocrinology has emerged as a novel science. Disturbances in either of these systems invariably lead to significant changes in other compartments. There are no types of pathology that would not involve all three parts of entire system. The unity of all components of the system clearly manifests in stress, traumatic shock, and cytokine storm. Of particular interest is the cross-usage of drugs applied in therapy of disorders affecting either of three systems. The use of immunotropic drugs has found application in the treatment of psychiatric disorders. Methods of pharmacological action on macrophages are being developed for treatment of endocrine disorders. Thus, sufficient evidence has been accumulated to consider the immune, nervous and endocrine systems as a common system of physiological regulation, which seems to be based on transmission and processing of information.</p></abstract><trans-abstract xml:lang="ru"><p>В обзоре представлена история эволюции взглядов на взаимосвязь иммунной, нервной и эндокринной систем и приводятся аргументы, обосновывающие концепцию, что они представляют собой компоненты единой регуляторной системы, поскольку их структуры плотно интегрированы друг в друга, в качестве сигнальных молекул они используют одни и те же биологически активные вещества. При этом одна и та же молекула в зависимости от клетки, ее образующей, может быть отнесена либо к нейротрансмиттерам, либо гормонам, либо цитокинам. На периферических нейронах и нервных окончаниях вагуса обнаружены рецепторы к цитокинам, а IL-4 регулирует синаптическую передачу. Доказана функция клеток иммунной системы продуцировать гормоны и нейропептиды. Катехоламины могут происходить из клеток иммунной системы. Гипоталамические же нейросекреторные клетки экспрессируют IL-1, а клетки астроцитарной глии – интерферон. В регуляции функций всегда выступают вместе, дополняя или замещая друг друга, имеют общий координационный центр. Так, передняя доля гипофиза, секретируя гормон роста, влияет на синтез и секрецию тимулина эпителиальными тимическими клетками. Таким образом формируется гипоталамо-гипофизарно-тимическая ось. Появилась новая наука – нейроиммуноэндокринология. Патология одной из систем неизменно приводит к существенным изменениям и в других. Нет ни одного вида патологии, в которой не были бы задействованы все три компонента единой системы. Наиболее ярко единство всех копонентов системы проявляется при стрессе, травматическом шоке, цитокиновом шторме. Особый интерес представляет перекрестное применение препаратов в терапии заболеваний каждой из трех систем. Использование иммунотропных препаратов нашло применение в лечении психических расстройств. Разрабатываются методы фармакологического воздействия на макрофаги при лечении эндокринных расстройств. Таким образом, накоплено достаточное количество фактов, дающих основание рассматривать иммунную, нервную и эндокринную системы в качестве единой системы физиологической регуляции, основой которой считается передача и переработка информации.</p></trans-abstract><kwd-group xml:lang="en"><kwd>neuro-immune-endocrine system</kwd><kwd>macrophages</kwd><kwd>APUD-system</kwd><kwd>thymus</kwd><kwd>regulation of functions</kwd><kwd>hypothalamic-pituitary-thymic axis</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>нейроиммуноэндокринная система</kwd><kwd>макрофаги</kwd><kwd>APUD-система</kwd><kwd>тимус</kwd><kwd>регуляция функций</kwd><kwd>гипоталамо-гипофизарно-тимическая ось</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="ru">Министерство науки и высшего образования Российской Федерации</institution></institution-wrap><institution-wrap><institution xml:lang="en">Ministry of Science and Higher Education of the Russian Federation</institution></institution-wrap></funding-source><award-id>075-03-2022-352</award-id></award-group></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Абрамов В.В. 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