mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-SSP-1862mimmun-1862Research ArticleОБЗОРЫREVIEWSСептический шок: перспективные методы диагностики и лечения на основе иммунопатогенезаSeptic shock: perspective methods of diagnostics and therapy based on immunopathogenesisГомановаЛ. И.GomanovaL. I.

Гоманова Лилия Ильинична – Студентка Института общественного здоровья

119991, Россия, Москва, ул. Трубецкая, 8Teл.: 8 (919) 109-95-90.

Student, Institute of Public Health

119991, Russian Federation, Moscow, Trubetskaya str., 8Phone: 7 (919) 109-95-90.

gomanov@list.ruФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения РФ (Сеченовский университет)РоссияFirst Moscow State I. Sechenov Medical University (Sechenov University)Russian Federation202020052020223459472Copyright © Гоманова Л.И., 20202020Гоманова Л.И.Gomanova L.I.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/1862

На основе III Международного консенсуса в отношении определения сепсиса и септического шока (Sepsis-3) было признано современное определение септического шока: «Септический шок – это разновидность сепсиса, который сопровождается выраженными гемодинамическими, метаболическими и клеточными расстройствами, причем эти нарушения ассоциируются с более высоким риском летального исхода». Несмотря на классическое представление о развитии септического шока (провоспалительный, иммуносупрессивный этапы и стадия полиорганной недостаточности с формированием шоковых органов), теории активации каспазного пути, эндоканнабиноидной системы и системы белка запрограммированной клеточной смерти 1 (Programmed cell death 1 – PD-1) в формировании септического шока являются перспективными подходами в разработке новых диагностических и терапевтических методов. Уже на ранней стадии септического шока наблюдается лимфопения, которая в дальнейшем приводит к глубокой иммуносупрессии. Проводимые ранее исследования по лечению разрабатывали методы снижения провоспалительной стадии, что не давало должного результата среди пациентов. Сейчас необходимо искать пути ингибирования апоптоза, истощения лимфоцитов, макрофагов и других иммунных клеток человека в ходе развития септического шока. Известно, что каспазы опосредуют врожденное обнаружение патогенных микроорганизмов, вызывают пироптоз, активацию моноцитов. Доказано, что ингибирование каспаз-8, каспаз-11 приводит к снижению функционирования моноцитов и высвобождения цитокинов, что играет важную роль в иммунопатогенезе септического шока. Также показаны ассоциации экспрессии PD-1 и PD-2 на лимфоцитах CD4 + и моноцитах с развитием иммунных дисфункций, снижением пролиферации лимфоцитов и повышением концентрации интерлейкина-10. Стимуляция эндоканнабиноидных рецепторов способна ослаблять воспаление, ингибируя цитопатическое и имуннодепрессивное действие патогенов. Показано, что классические биомаркеры септического шока (провоспалительные, противовоспалительные цитокины; прокальцитонин, лактат и др.) не обладают высокой прогностической силой по отношению к исходу заболевания. Циркулирующие и цитрулированные гистоны плазмы крови, определяемые с помощью масс-спектрометрии, могут служить потенциальными диагностическими маркерами септического шока, однако они требуют дальнейшего изучения. Применение окисленного фосфолипида oxPAPC (Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine), сульфида водорода и белков, связывающих жирные кислоты Fasciola hepatica (печеночная двуустка), предотвращает окислительный стресс, синтез провоспалительных цитокинов и обеспечивает созревание макрофагов и дендритных клеток. Дальнейшее изучение иммуннологических реакций в ходе септического шока имеет большое значение для обоснования новых подходов диагностики и терапии септического шока.

Based on the III International Consensus on the definition of Sepsis and Septic Shock (Sepsis-3), the modern definition of septic shock was proposed: “Septic shock is a type of sepsis that is accompanied by severe hemodynamic, metabolic and cellular disorders, and these disorders are associated with a higher risk fatal outcome”. Despite the classic idea of septic shock development (proinflammatory, immunosuppressive phases and, finally, multiple organ failure with distinct shock organs), the theory of activation of the caspase, endocannabioid system and system of protein of programmed death-1 in evolving septic shock are promising approaches to development of new diagnostic and therapeutic methods. Lymphopenia is already observed at an early stage of septic shock, which further leads to deep immunosuppression. Previous experimental studies have revealed some treatment methods to reduce the pro-inflammatory stage, which, however, did not show desired results in clinics. Now it is necessary to look for ways to inhibit apoptosis, depletion of lymphocytes, macrophages and other immune cells in the course of septic shock. It is known that caspases mediate innate detection of pathogenic microorganisms, cause pyroptosis, activation of monocytes. It has been proven that inhibition of caspase-8, caspase-11 leads to decreased monocyte functioning and cytokine release, which plays an important role in immunopathogenesis of septic shock. Associations of PD-1 and PD-2 expression on CD4+  lymphocytes and monocytes are also shown to be connected with immune dysfunctions, decrease in lymphocyte proliferation, and increased interleukin-10 concentration. Stimulation of the cannabinoid receptors is able to reduce inflammation by inhibiting cytopathic and immunosuppressive effects of pathogens. It has been shown that classic septic shock biomarkers (pro-inflammatory, anti-inflammatory cytokines; procalcitonin, lactate, etc.) do not have predictive power in relation to the outcome of the disease. Circulating and citrullated histones, determined by mass spectrometry, may serve as potential diagnostic markers of septic shock, but they require further study. Use of oxidized phospholipid oxPAPC (Oxidized 1-palmitoyl-2-arachidonoyl-snglycero-3-phosphocholine), hydrogen sulfide and Fasciola hepatica fatty acid binding proteins (hepatic fluke) prevents oxidative stress, synthesis of pro-inflammatory cytokines and provides maturation of macrophages and dendritic cells. Further study of immunological reactions during septic shock is of great importance for substantiation of new approaches to the diagnostics and therapy of septic shock.

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