Cytokines and inflammationCytokines and inflammationЦитокины и воспаление1684-7849Eco-Vector62730110.17816/CI627301ReviewsНаучные обзорыReview ArticleCytokine regulation disbalance: the basis for COVID-19 immunopathogenesisДисбаланс цитокиновой регуляции — основа иммунопатогенеза COVID-19https://orcid.org/0000-0002-8228-42402064-7584SimbirtsevAndrey S.СимбирцевАндрей Семенович
Russian Federation

MD, Dr. Sci. (Medicine), Professor, Corresponding Member of the Russian Academy of Sciences

д-р мед. наук, профессор, член-корреспондент РАН

simbas@mail.ruState Research Institute of Highly Pure BiopreparationsГосударственный научно-исследовательский институт особо чистых биопрепаратов090420241812202320212232102202407032024Copyright ©; 2023, Simbirtsev A.S.Copyright ©; 2023, Симбирцев А.С.2023Simbirtsev A.S.Симбирцев А.С.https://cijournal.ru/1684-7849/article/view/627301

Coronavirus infection activates two main signaling pathways for type I and III IFN and the gene expression and synthesis of proinflammatory cytokines. These cytokines are required for antiviral defense and inflammatory reaction formation. SARS-CoV-2 coronavirus could inhibit the IFN system by depressing signaling pathways for IFN gene expression, synthesis, and secretion. IFN inhibition should be considered the primary reason for coronavirus escape from the immune system and a key factor for COVID-19 immunopathogenesis. Cytokine regulation disbalance in patients with severe COVID-19 is closely associated with low and delayed IFN synthesis, while proinflammatory cytokine production by macrophages and T-lymphocytes continues simultaneously with intensive virus replication. Thus, the reason for COVID-19 immunopathogenesis is the cytokine regulation disbalance where IFN inhibition and intensive proinflammatory cytokine synthesis lead to cytokine storm, inadequate inflammation, respiratory distress syndrome development, respiratory failure, systemic inflammatory complications, and polyorganic failure.

В ответ на инфицирование клеток верхних дыхательных путей коронавирусом запускаются два основных сигнальных пути активации экспрессии генов и синтеза интерферона (IFN) I и III типов, а также провоспалительных цитокинов, призванных обеспечить противовирусную защиту и организовать защитную воспалительную реакцию. Однако коронавирус SARS-CoV-2 способен подавлять систему IFN, вмешиваясь в клеточный сигналинг на разных этапах активации экспрессии генов, синтеза и секреции IFN. Подавление системы эндогенного IFN является причиной ускользания коронавируса от защитных механизмов иммунной системы, что можно считать ключевым фактором иммунопатогенеза коронавирусной инфекции. Дисбаланс цитокиновой регуляции при тяжёлых формах COVID-19 связан с тем, что на фоне низкого и отсроченного синтеза IFN провоспалительные цитокины в ответ на безудержную репликацию вируса продолжают синтезироваться макрофагами и Т-лимфоцитами в больших количествах, приводя к развитию цитокинового шторма. Вследствие этого иммунопатогенез COVID-19 связан с развитием несбалансированного иммунного ответа в результате подавления коронавирусом SARS-CoV-2 синтеза IFN и компенсаторной гиперпродукции провоспалительных цитокинов, служащей причиной неадекватно сильного воспаления с развитием острого респираторного дистресс-синдрома и дыхательной недостаточности с последующим развитием системных воспалительных проявлений и полиорганной недостаточности.

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