scbmtБИОМЕДИЦИНАJournal Biomed2074-59822713-0428Scientific center of biomedical technologies of Federal Medical and Biological Agency10.33647/2074-5982-16-4-14-23scbmt-1214Research ArticleРЕГУЛЯТОРНЫЕ ОПИОИДНЫЕ ПЕПТИДЫREGULATORY OPIOID PEPTIDESОпиоидэргическая система иммунных клеток: новая фармакологическая мишень в терапии «цитокинового шторма»The Opioidergic System of Immune Cells: A New Pharmacological Target in the Therapy of “Cytokine Storm”КаркищенкоВ. Н.KarkischenkoV. N.

Каркищенко Владислав Николаевич, д.м.н., проф.

143442, Московская обл., Красногорский р-н, п. Светлые горы, владение 1

Vladislav N. Karkischenko, Dr. Sci. (Med.), Prof.

143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1

scbmt@yandex.ruПомыткинИ. А.PomytkinI. A.

Помыткин Игорь Анатольевич, к.х.н.

143442, Московская обл., Красногорский р-н, п. Светлые горы, владение 1

Igor A. Pomytkin, Cand. Sci. (Chem.)

143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1

ipomytkin@mail.ruСкворцоваВ. И.SkvortsovaV. I.

Скворцова Вероника Игоревна, д.м.н., проф., чл.-корр. РАН

123182, Москва, Волоколамское шоссе, д. 30

Veronika I. Skvortsova, Dr. Sci. (Med.), Prof., Corresponding Member of the Russian Academy of Sciences

123182, Moscow, Volokolamskoye highway, 30

priemnaya@fmba.gov.ruФГБУН «Научный центр биомедицинских технологий Федерального медико-биологического агентства России»РоссияScientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of RussiaRussian FederationФедеральное медико-биологическое агентство РоссииРоссияFederal Medical and Biological Agency of RussiaRussian Federation2020151020201641423Copyright © Каркищенко В.Н., Помыткин И.А., Скворцова В.И., 20202020Каркищенко В.Н., Помыткин И.А., Скворцова В.И.Karkischenko V.N., Pomytkin I.A., Skvortsova V.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.scbmt.ru/jour/article/view/1214

В настоящей статье предложен новый фармакологический подход к подавлению «цитокинового шторма», основанный на использовании опиоидных пептидов. Клетки иммунной системы имеют полноценную опиоидную систему сигнализации, состоящую из всех трех типов опиоидных рецепторов: мю (μ), дельта (δ) и каппа (κ). Эти клетки также экспрессируют проопиомеланокортин, проэнкефалин и продинорфин, являющиеся предшественниками агонистов рецепторов β-эндорфина, метэнкефалина и динорфинов соответственно. Особенностью опиоидной системы иммуноцитов является то, что экспрессия всех компонентов этой системы повышается в ответ на действие цитокинов и воспаление, что указывает на ее участие в регуляции иммунного ответа. Недавно было показано, что динорфины, возможно, играют важную роль в ингибировании экспрессии провоспалительных цитокинов иммунными клетками, подавляя транслокацию активного димера ядерного фактора каппа В (NF-κB). С учетом ключевой роли канонического пути активации NF-κB в экспрессии цитокинов, который реализуется при активации множества различных рецепторов, подавление этого пути с использованием опиоидных пептидов обеспечивает новый фармакологический подход к решению проблемы «цитокинового шторма». Актуальность этого подхода связана с пандемией коронавирусной инфекции COVID-19, роль «цитокинового шторма» в которой установлена многочисленными исследованиями.

This article proposes a new pharmacological approach to suppressing “cytokine storm” syndromes based on the use of opioid peptides. Immune cells possess a complete opioid signaling system consisting of all three types of opioid receptors: mu (μ), delta (δ) and kappa (κ). These cells also express proopiomelanocortin, proenkephalin and prodinorphin, which serve as precursors for such receptor agonists as β-endorphin, methenkephalin and dynorphins, respectively. A distinct feature of the opioid system of immunocytes consists in an increased expression of all its components in response to the action of cytokines and inflammation, which indicates participation of this system in regulating the immune response. It has been recently shown that dynorphins are likely to play an important role in inhibiting the expression of proinflammatory cytokines by immune cells through impeding the translocation of the active nuclear factor kappa B (NF-κB) dimer. Given the key role of the canonical pathway of NF-κB activation in cytokine expression realized when activating a variety of receptors, suppression of this pathway using opioid peptides provides a new pharmacological approach to solving the “cytokine storm” problem. The relevance of this approach is associated with the COVID-19 coronavirus infection pandemic, the role of the “cytokine storm” in which has been established by numerous studies.

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