rmtОбщая реаниматологияGeneral Reanimatology1813-97792411-7110FSBI "SRIGR" RAMS10.15360/1813-9779-2020-3-16-33rmt-1917Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ И ПРАКТИКАCLINICAL STUDIES AND PRACTICEПрогностическое значение генетического полиморфизма промоторной области AQP5 при сепсисе с различными очагамиPrognostic Value of a Genetic Polymorphism in Promotor Region of AQP5 in Sepsis Depends on the Source of InfectionПисаревВ. М.PisarevV. M.

Владимир Митрофанович Писарев

107031, г. Москва, ул. Петровка, 2, д. 5, стр. 2

Vladimir M. Pisarev

25 Petrovka Str., Bldg. 2, 107031 Moscow

vpisarev@gmail.comЧумаченкоА. Г.ChumachenkoA. G.

107031, г. Москва, ул. Петровка, 2, д. 5, стр. 2

Anastasiya G. Chumachenko

25 Petrovka Str., Bldg. 2, 107031 Moscow

ТюринИ. Н.TurinI. N.

127083, Москва, ул. Касаткина, д. 7

Igor N. Turin

7 Kasatkina Str, 127083 Moscow

ЧерпаковР. А.CherpakovR. A.

127083, Москва, ул. Касаткина, д. 7

Rostislav A. Cherpakov

7 Kasatkina Str, 127083 Moscow

ЕлисинаЕ. В.ElisinaE. V.

107031, г. Москва, ул. Петровка, 2, д. 5, стр. 2

Elizaveta V. Elisina

25 Petrovka Str., Bldg. 2, 107031 Moscow

ГригорьевЕ. К.GrigorievE. K.

107031, г. Москва, ул. Петровка, 2, д. 5, стр. 2

Evgeny K. Grigoriev

25 Petrovka Str., Bldg. 2, 107031 Moscow

АлександровИ. А.AleksandrovI. A.

117997, Москва, ул. Саморы Машела, д. 1

Ivan A. Aleksandrov

1 Samora Mashela Str., 117997 Moscow

ТутельянА. В.TutelyanA. V.

117997, Москва, ул. Саморы Машела, д. 1; 111123, Москва, ул. Новогиреевская, д. 3а

Aleksey V. Tutelyan

1 Samora Mashela Str., 117997 Moscow; 3a Novogireyevskaya Str., 111123 Moscow

НИИ общей реаниматологии им. В. А. Неговского, ФНКЦ РРРоссияV A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and RehabilitologyRussian FederationГородская клиническая больница № 40 Департамента здравоохранения г. МосквыРоссияCity Clinical Hospital № 40Russian FederationНациональный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Д. Рогачева Минздрава РоссииРоссияRogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of RussiaRussian FederationНациональный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Д. Рогачева Минздрава России; Центральный НИИ эпидемиологии РоспотребнадзораРоссияRogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russia; Central Research Institute of Epidemiology of RospotrebnadzorRussian Federation2020040720201631633Copyright © Писарев В.М., Чумаченко А.Г., Тюрин И.Н., Черпаков Р.А., Елисина Е.В., Григорьев Е.К., Александров И.А., Тутельян А.В., 20202020Писарев В.М., Чумаченко А.Г., Тюрин И.Н., Черпаков Р.А., Елисина Е.В., Григорьев Е.К., Александров И.А., Тутельян А.В.Pisarev V.M., Chumachenko A.G., Turin I.N., Cherpakov R.A., Elisina E.V., Grigoriev E.K., Aleksandrov I.A., Tutelyan A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.reanimatology.com/rmt/article/view/1917

Аквапорины — мембранные белки, играющие роль в транспорте молекул воды через клеточную мембрану и участвующие в формировании и разрешении отеков, миграции клеток, воспалительных реакциях. Имеются единичные исследования, свидетельствующие о связи генетического полиморфизма аквапорина 5 (rs3759129 AQP5) с течением сепсиса. Вместе с тем, очевидная гетерогенность пациентов по очагам инфекции может затруднить поиск наиболее выраженной ассоциации генотипов AQP5 с течением инфекционных осложнений критических состояний и дальнейшую разработку rs3759129 AQP5 как потенциально сильного маркера исхода сепсиса.

Цель исследования

Цель исследования: выяснить связь аллельных вариантов сайта однонуклеотидного полиморфизма гена AQP5 (1364A/C, rs3759129) с исходами сепсиса (СЕПСИС-3, 2016) в зависимости от вероятного первичного очага инфекции.

Материалы и методы

Материалы и методы. С помощью тетрапраймерной полимеразной цепной реакции с последующей электрофоретической визуализацией продуктов проведено аллель-специфическое генотипирование ДНК, выделенной из образцов крови 339 пациентов отделений реанимации и интенсивной терапии двух лечебных учреждений.

Результаты

Результаты. Выявлена тенденция к преимущественному выживанию пациентов с сепсисом с генотипами AQP5 «С+» (AС и CC) вне зависимости от источника инфекции (p>0,050). Однако только в группе пациентов с генотипами AQP5 AC или CC и абдоминальным сепсисом (Sepsis-3, 2016) было вы

явлено значительное увеличение 30-дневной выживаемости по сравнению с гомозиготными пациентами генотипа AQP5 АА (p=0,002).

Заключение

Заключение. Информативная ценность выявления генотипов CC или AC AQP5 для прогноза 30дневной выживаемости по сравнению с гомозиготными пациентами с генотипом AA может быть выше у пациентов с абдоминальным сепсисом.

Aquaporins represent proteins contributed to water transport through cell membrane. They are involved in formation and resolution of edema, cell migration and inflammatory reaction. There are only few studies linking the genetic polymorphism of aquaporin 5 (rs3759129 AQP5) and sepsis. At the same time, the apparent heterogeneity of patients along the foci of infection may limit finding the most significant association of AQP5 genotypes with the course of infectious complications of critical conditions and restrict further development of rs3759129 AQP5 as a potentially strong marker of sepsis outcome.

The purpose of the study was to determine whether the preferential localization of the infection affects the prognostic value of the genetic marker AQP5 (1364A/C, rs3759129) in outcome prediction in sepsis (SEPSIS-3, 2016) patients.

Materials and methods

Materials and methods. Study groups (n=339) included ICU patients with abdominal sepsis (AS, including pancreatitits, peritonitis, cholecystitis, appendicitis; n=94) sepsis patients with other sources of infections  (n=65) and ICU patients without sepsis (n=180). AQP5 polymorphism was studied by analyzing PCR products in a 2% agarose gel using a AQP5 1364A/C specific tetra primer set.

Result

Result. Distribution of alleles (A and C) and genotypes (AA, AC and CC) AQP5 1364A/C in patients with  sepsis or sepsis subgroups (sepsis with no septic shock and sepsis shock patients) versus control group (healthy  volunteers) did not differ. Although there was a trend to preferential survival of sepsis patients with genotype C AQP5 despite the source of infection, only patients with AQP5 CC or AC genotype and abdominal sepsis (Sepsis-3), or a subgroup of the same AQP5 genotype experiencing septic shock, demonstrated increased 30day survival versus AA homozygotic patients (P=0.002).

Conclusion

Conclusion. The informative value of detecting the AQP5 CC or AC genotype for prognosis of 30-day survival versus AA homozygotic patients is most significant only in abdominal sepsis patients.

полиморфизм геновAQP5rs3759129сепсисабдоминальный сепсискритические состоянияSNPgenetic polymorphismAQP5aquaporinssepsiscritical illnessРабота выполнена в рамках темы госзадания № 0563-2019-0018 (рук. темы ВМП). Авторы выражают признательность д. м. н., проф. М. В. Петровой (ФНКЦ РР) за организацию сбора биоматериалов и клинического анализа данных пациентов. Частично результаты работы доложены на 39-м Международного симпозиума по интенсивной медицине и медицине скорой помощи (ISICEM) в 2019 г. [58]The work was carried out as a part of the state assignment No. 0563-20190018 from the Ministry of Science and High Education of Russian Federation (to VMP). The authors would like to express their gratitude to professor Marina V. Petrova (Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitol-ogy) for organizing the collection of biomaterials and clinical analysis of patients data. Partly, the results were reported at the 39th International Symposium on Intensive and Emergency Medicine (ISICEM) in 2019 [58]ReferencesAngus D.C., van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013; 369 (9): 840–851. DOI: 10.1056/NEJMra1208623Angus D.C., van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013; 369 (9): 840-851. DOI: 10.1056/NEJMra1208623Machado F.R., Nsutebu E., AbDulaziz S. et al. Sepsis 3 from the perspective of clinicians and quality improvement initiatives. J. Crit Care. 2017; 40: 315–317. Epub 2017 Apr 26, DOI: 10.1016/j.jcrc.2017.04.037Machado FR., Nsutebu E., AbDulaziz S. Sepsis 3 from the perspective of clinicians and quality improvement initiatives. J. Crit Care. 2017; 40: 315-317. Epub 2017 Apr 26, DOI: 10.1016/j.jcrc.2017.04.037Белобородова Н.В., Острова И.В. Сепсис-ассоциированная энцефалопатия (обзор). Общая реаниматология. 2017; 13 (5): 121-139. DOI: 10.15360/1813-9779-2017-5-121-139.Beloborodova N.B., Ostrova I.V Sepsis-Associated Encephalopathy (Review). General Reanimatology=Obshchaya Reanimatologiya. 2017; 13 (5): 121-139. [In Russ.]. DOI: 10.15360/1813-9779-2017-5-121-139Кавайон Ж. Новые методы лечения при сепсисе: модели на животных «не работают» (обзор). Общая реаниматология. 2018; 14 (3): 46-53. DOI: 10.15360/1813-9779-2018-3-46-53.Cavaillon J. New Approaches to Treat Sepsis: Animal Models «Do Not Work» (Review). General Reanimatology=Obshchaya Reanimatologiya. 2018; 14 (3): 46-53 [In Russ.]. DOI: 10.15360/1813-9779-2018-3-46-53.Уша.кова Н.Д., Кит О.И., Маслов А.А., Меньшенина А.П. Экстракорпоральная детоксикация при абдоминальном сепсисе у онкологических больных Общая реаниматология. 2018; 14 (2): 25-34. DOI: 10.15360/1813-9779-2018-2-25-34Ushakova N.D., Kit O.I., MaslovAA., MensheninaA.P Extracorporeal Detoxification in Abdominal Sepsis in Cancer Patients. General Rea-nimatology=Obshchaya Reanimatologiya. 2018; 14 (2): 25-34 [In Russ.]. DOI: 10.15360/1813-9779-2018-2-25-34Verkman A.S. Aquaporins in clinical medicine. Annu Rev Med. 2012; 63: 303-316. DOI: 10.1146/annurev-med-043010-193843Verkman A.S. Aquaporins in clinical medicine. Annu Rev Med. 2012; 63: 303-316. DOI: 10.1146/annurev-med-043010-193843Rump K, UnterbergM., Bergmann L., Bankfalvi A., Menon A., Schafer S, Scherag A., Bazzi Z., Siffert W., Peters J., AdamzikM. AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study. J Transl Med. 2016 Nov 21; 14 (1): 321. PMID: 27871297 DOI: 10.1186/s12967-016-1079-2Rump K., Unterberg M., Bergmann L., Bankfalvi A., Menon A., Schafer S., Scherag A., Bazzi Z., Siffert W., Peters J., Adamzik M. AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and immune cell migration: a prospective laboratory and patient study. J Transl Med. 2016 Nov 21; 14 (1): 321. PMID: 27871297 DOI: 10.1186/s12967-016-1079-2Rump K., Adamzik M. Function of aquaporins in sepsis: a systematic review. CellBiosci. 2018; 8: 10. DOI: 10.1186/s13578-018-0211-9Rump K., AdamzikM. Function of aquaporins in sepsis: a systematic review. Cell Biosci. 2018; 8: 10. DOI: 10.1186/s13578-018-0211-9Тюрин И.Н., Раутбарт С.А., Козлов И.А. Ранние особенности кровообращения у больных с неблагоприятным исходом абдоминального сепсиса (предварительное сообщение). Общая реаниматология. 2017; 13 (3): 13-24. DOI: 10.15360/1813-9779-2017-3-13-24Tyurin I.N., Rautbart S.A., Kozlov I.A. Early Characteristics of Circulation in Patients with Poor Outcome of Abdominal Sepsis (Preliminary Report). General Reanimatology=Obshchaya Reani-matologiya. 2017; 13 (3): 13-24 [In Russ.]. DOI: 10.15360/1813-9779-2017-3-13-24Russell JA. Genomics and pharmacogenomics of sepsis: so close and yet so far. CritCa. re. 2016; 20 (1): 185. DOI: 10.1186/s13054-016-1374-6Russell J.A. Genomics and pharmacogenomics of sepsis: so close and yet so far. Crit Care. 2016; 20 (1): 185. DOI: 10.1186/s13054-016-1374-6Смелая Т.В., Кузовлев А.Н., Мороз В.В., Голубев А.М., Белопольская О.Б., Сальникова Л.Е. Молекулярно-генетические маркеры нозокомиальной пневмониии острого респираторного дистресссиндрома. Общая реаниматология. 2015; 11 (3): 24-38. DOI: 10.15360/1813-9779-2015-3-24-38Smelaya T. V, Kuzovlev A.N., Moroz VV, Golubev A.M., Belopolskaya O.B., Salnikova L.E. Search for Common Molecular Genetic Markers of Nosocomial Pneumonia and Acute Respiratory Distress Syndrome. General Reanimatology=Obshchaya Reanimatologiya. [In Russ.]. DOI: 10.15360/1813-9779-2015-3-24-38МязинА.Е., ЧумаченкоА.Г, КузовлевА.Н., ГолубевА.М., МорозВ.В., Га,понов А.М., Тутельян А.В., Голубев МА., Писарев В.М. Генетические варианты интронной области гена аквапорина aqp5 и развитие отека легких при легочной инфекции, осложненной септическим шоком. Общая реаниматология. 2016; 12 (3): 8-23. DOI: 10.15360/1813-9779-2016-3-8-23MyazinA.E., Chumachenko A.G., KuzovlevA.N., GolubevA.M., Moroz V.V., GaponovA.M., TutelianA.V., GolubevMA., Pisarev V.M. Genetic Variants of Intron Region of Aquaporin AQP5 Gene and Development of Pulmonary Edema in Lung Infection Complicated by Septic Shock. General Reanimatology=Obshchaya Reanimatologiya. 2016; 12 (3): 8-23 [In Russ.]. DOI: 10.15360/1813-9779-2016-3-8-23Ada.mzik M., Frey U.H., Mohlenkamp S., Scherag A., Waydhas C., MarggrafG., Dammann M., Steinmann J., Siffert W., Peters J. Aquapo-rin 5 gene promoter—1364A/C polymorphism associated with 30-day survival in severe sepsis. Anesthesiology. 2011; 114 (4): 912-917. DOI: 10.1097/ALN.0b013e31820ca911. PMID: 21427539Adamzik M., Frey U.H., Mohlenkamp S., Scherag A., Waydhas C., MarggrafG., Dammann M., Steinmann J., Siffert W., Peters J. Aquapo-rin 5 gene promoter—1364A/C polymorphism associated with 30-day survival in severe sepsis. Anesthesiology. 2011; 114 (4): 912-917. DOI: 10.1097/ALN.0b013e31820ca911. PMID: 21427539Rahmel T., Rump K., Peters J., Adamzik M. Aquaporin 5 -1364A/C Promoter Polymorphism Is Associated with Pulmonary Inflammation and Survival in Acute Respiratory Distress Syndrome. Anesthesiology. 2019; 130 (3): 404-413. DOI: 10.1097/ALN.0000000000002560Rahmel T., Rump K., Peters J., Adamzik M. Aquaporin 5 -1364A/C Promoter Polymorphism Is Associated with Pulmonary Inflammation and Survival in Acute Respiratory Distress Syndrome. Anesthesiology. 2019; 130 (3): 404-413. DOI: 10.1097/ALN.0000000000002560,La.mbertz N., HindyN.E., Adler C., Adamzik M., Keyvani K., Bankfalvi A., Siffert IW, Sandalcioglu E., Bachmann S.H. EXpression of aquaporin 5 and the AQP5 polymorphism A (-1364)C in association with peritumoral brain edema in meningioma patients. J Neurooncol. 2013; 112 (2): 297-305. DOI: 10.1007/s11060-013-1064-z. Epub 2013 Feb 8. PMID: 23392848Lambertz N., Hindy N.E., Adler C., AdamzikM., Keyvani K., Bankfalvi A., Siffert I W., Sandalcioglu E., Bachmann S.H. Expression of aqua-porin 5 and the AQP5 polymorphism A (-1364)C in association with peritumoral brain edema in meningioma patients. J Neurooncol. 2013; 112 (2): 297-305. DOI: 10.1007/s11060-013-1064-z. Epub 2013 Feb 8. PMID: 23392848Adamzik M., Frey U.H., Bitzer K., Jakob H., Baba H.A., Schmieder R. E., Schneider M.P., Heusch G., Peters J., Siffert W. A novel-1364A/C aquaporin 5 gene promoter polymorphism influences the responses to salt loading of the renin-angiotensin-aldosterone system and of blood pressure in young healthy men. Basic Res Cardiol. 2008; 103: 598-610. DOI: 10.1007/s00395-008-0750-z PMID: 18846354Adamzik M., Frey U.H., Bitzer K., Jakob H., Baba H.A., Schmieder R. E., Schneider M.P., Heusch G., Peters J., Siffert W. A novel-1364A/C aquaporin 5 gene promoter polymorphism influences the responses to salt loading of the renin-angiotensin-aldosterone system and of blood pressure in young healthy men. Basic Res Cardiol. 2008; 103: 598-610. DOI: 10.1007/s00395-008-0750-z PMID: 18846354ZhangZ.Q., Song Y.L., Chen Z.H., Shen Y., Bai C-X Deletion of aquaporin 5 aggravates acute lung injury induced by Pseudomonas aeruginosa. J Trauma 2011; 71: 1305-1311 DOI: 10.1097/TA.0b013e3182128528,ZhangZ.Q., Song Y.L., Chen Z.H., Shen Y., Bai C-X Deletion of aqua-porin 5 aggravates acute lung injury induced by Pseudomonas aeruginosa. J Trauma 2011; 71: 1305-1311 DOI: 10.1097/TA.0b013e 3182128528SingerM., Deutschma.n C.S., Seymour C.W., Manu Shankar-Hari M., Anna. ne D., Bauer M., Bellomo R., Bernard G. R., Chiche J-L., Coopers-mith C.M., HotchkissR.S., Levy M.M., MarshallJ.C., Martin G.S., Opal S. M., Rubenfeld G.D., van der Poll T., Angus D.C. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA.. 2016; 315 (8): 801-810. DOI: 10.1001/jama.2016.0287Singer M., Deutschman C.S., Seymour C.W., Manu Shankar-Hari M., Annane D., Bauer M., Bellomo R., Bernard G. R., Chiche J-L., Coopers-mith C.M., HotchkissR.S., LevyM.M., MarshallJ.C., Martin G.S., Opal S. M., Rubenfeld G.D., van der Poll T., Angus D.C. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315 (8): 801-810. DOI: 10.1001/jama.2016.0287Сальникова Л.Е., Чумаченко А.Г., Веснина И.Н., Лаптева Н.Ш., Кузнецова Г.И., Абилев С.К., Рубанович А.В. Полиморфизм генов репарации и цитогенетические эффекты облучения. Радиационная биология. Радиоэкология. 2010. Т. 50. № 6. С. 656-662. ISSN: 0869-8031, УДК [57+61]: 539.1.047: 575.224: 23SalnikovaL.E., Chumachenko A.G., VesninaI.N., LaptevaN.Sh., Kuznetsova G.I., Abilev S.K., Rubanovich A.V Polymorphism of repair genes and cytogenetic effects of radiation. Radiacionnaya biologiya. Radioekologiya. 2010; 50 (6): 656-662 [In Russ.]. ISSN: 0869-8031, УДК [57+61]: 539.1.047: 575.224: 23Khan A., Fornes O., Stigliani A., Gheorghe M., Castro-Mondragon J.A., va.n der Lee R., Bessy A., Cheneby J., Kulkarni S., Tan G., Baranasic D., Arenillas D., Sandelin A., Vandepoele K., Lenhard B., Ballester B., Was-serman W.W., Parcy F, Mathelier A. JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework. Nucleic Acids Res. 2018; 46: D260-D266, DOI: 10.1093/nar/gkx1126Khan A., Fornes O., Stigliani A., Gheorghe M., Castro-Mondragon J.A., van der Lee R., Bessy A., Cheneby J., Kulkarni S., Tan G., Baranasic D., Arenillas D., Sandelin A., Vandepoele K., Lenhard B., Ballester B., Was-serman W.W., Parcy F, Mathelier A. JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework. Nucleic Acids Res. 2018; 46: D260-D266, DOI: 10.1093/nar/gkx1126Kumar S., Ambrosini G., Bucher P. SNP2TFBS - a database of regulatory SNPs affecting predicted transcription factor binding site affinity, Nucleic Acids Res. 2017 Jan4. PMC5210548, DOI: 10.1093/nar/gkw1064,Kumar S., Ambrosini G., Bucher P. SNP2TFBS - a database of regulatory SNPs affecting predicted transcription factor binding site affinity, Nucleic Acids Res. 2017 Jan4. PMC5210548, DOI: 10.1093/nar/gkw1064,Li S.-L., Schlegel W., Valente A.J., ClarkRA. Critical flanking sequences of PU.1 binding sites in myeloid-specific promoters. The Journal of Biological Chemistry, Nov.5, 1999; DOI: 10.1074/jbc274.45.32453Li S.-L., Schlegel W., Valente A.J., Clark R.A. Critical flanking sequences of PU.1 binding sites in myeloid-specific promoters. The Journal of Biological Chemistry, Nov.5, 1999; DOI: 10.1074/jbc274.45.32453Song Y., Fukuda N., Bai C., Ma T., Matthay M.A., Verkman A.S. Role of aquaporins in alveolar fluid clearance in neonatal and adult lung, and in oedema formation following acute lung injury: studies in transgenic aquaporin null mice. JPhysiol. 2000; 525 Pt 3: 771-779. PMID: 10856128Song Y., Fukuda N., Bai C., Ma T., Matthay M.A., Verkman A.S. Role of aquaporins in alveolar fluid clearance in neonatal and adult lung, and in oedema formation following acute lung injury: studies in transgenic aquaporin null mice. J Physiol. 2000; 525 Pt 3: 771-779. PMID: 10856128ZhangZ., Chen Z., Song Y., Zhang P, Hu J., Bai C. Expression of aqua-porin 5 increases proliferation and metastasis potential of lung cancer. J Pathol. 2010; 221: 210-220. DOI: 10.1002/path.2702 PMID: 20455256Zhang Z., Chen Z., Song Y., Zhang P, Hu J., Bai C. Expression of aqua-porin 5 increases proliferation and metastasis potential of lung cancer. J Pathol. 2010; 221: 210-20. DOI: 10.1002/path.2702 PMID: 20455256Papadopoulos M.C., Saadoun S., Verkman A.S. Aquaporins and cell migration. Pflugers Arch. 2008; 456: 693-700. DOI: 10.1007/s00424-007-0357-5 PMID: 17968585,Papadopoulos M.C., Saadoun S., Verkman A.S. Aquaporins and cell migration. Pflugers Arch. 2008; 456: 693-700. DOI: 10.1007/s00424-007-0357-5 PMID: 17968585,Lerman Y.V., Kim M. Neutrophil migration under normal and sepsis conditions. Cardiovasc HematolDisordDrug Targets. 2015; 15: 19-28. DOI: 10.2174/1871529X15666150108113236. PMID: 25567338,Lerman Y.V., Kim M. Neutrophil migration under normal and sepsis conditions. Cardiovasc Hematol Disord Drug Targets. 2015; 15: 19-28. DOI: 10.2174/1871529X15666150108113236. PMID: 25567338,Castanheira S.F, Silva F.V.E., Ferreira R.G.,Kanashiro A., Gongalves Leite C.A.V., Nascimento D.C., Colon D.F., Borges V., Alves-Filho J-C., Queiroz Cunha F Paradoxical roles of the neutrophil in sepsis: protective and deleterious. Front Immunol. 2016; 7: 155. PMID: 27199981, DOI: 10.3389/fimmu.2016.00155,Castanheira S.F, Silva F.V.E., Ferreira R.G.,Kanashiro A., Gongalves Leite C.A.V., Nascimento D.C., Colon D.F., Borges V., Alves-Filho J-C., Queiroz Cunha F. Paradoxical roles of the neutrophil in sepsis: protective and deleterious. Front Immunol. 2016; 7: 155. PMID: 27199981, DOI: 10.3389/fimmu.2016.00155CraciunF.L., SchullerE.R., RemickD.G. Early enhanced local neutrophil recruitment in peritonitis-induced sepsis improves bacterial clearance and survival. J Immunol. 2010; 185: 6930-6938. DOI: 10.4049/jimmunol.1002300. PMID: 21041722,Craciun F.L., Schuller E.R., Remick D.G. Early enhanced local neutrophil recruitment in peritonitis-induced sepsis improves bacterial clearance and survival. J Immunol. 2010; 185: 6930-6938. DOI: 10.4049/jimmunol.1002300. PMID: 21041722Rahmel T., Nowak H., Rump K., Siffert W., Peters J., Adamzik M. The aquaporin 5 -1364A/C promoter polymorphism impacts on resolution of acute kidney injury in pneumonia evoked ARDS. PLoS One. 2018 Dec 5; 13 (12): e0208582. DOI: 10.1371/journal.pone.0208582,Rahmel T., Nowak H., Rump K., Siffert W., Peters J., Adamzik M. The aquaporin 5 -1364A/C promoter polymorphism impacts on resolution of acute kidney injury in pneumonia evoked ARDS. PLoS One. 2018 Dec 5; 13 (12): e0208582. DOI: 10.1371/journal.pone.0208582Leligdo wicz A., Dodek P.M., No rena M., Wong H., Kumar A., Kumar A., Cooperative Antimicrobial Therapy of Septic Shock Database Research Group. Association between source of infection and hospital mortality in patients who have septic shock. Am J Respir Crit Care Med. 2014; 189 (10): 1204-1213 PMID: 24635548 DOI: 10.1164/rccm.201310-1875OCLeligdo wicz A., Dodek PM., No rena M., Wong H., Kumar A., Kumar A., Cooperative Antimicrobial Therapy of Septic Shock Database Research Group. Association between source of infection and hospital mortality in patients who have septic shock. Am J Respir Crit Care Med. 2014; 189 (10): 1204-1213 PMID: 24635548 DOI: 10.1164/rccm.201310-1875OCCahill R.A, Wa.ng J.H, Redmond H.P Enteric bacteria and their antigens may stimulate postoperative peritoneal adhesion formation. Surgery. 2007; 141: 403-410. DOI: 10.1016/j.surg.2006.09.010Cahill R.A, Wang J.H, Redmond H.P. Enteric bacteria and their antigens may stimulate postoperative peritoneal adhesion formation. Surgery. 2007; 141: 403- 410. DOI: 10.1016/j.surg.2006.09.010Karantonis F.F., Nikiteas N., Perrea D., Vlachou A., Giamarellos-Bo-urboulis E.J., Tsigris C., Kostakis A. Evaluation of the effects of laparotomy and laparoscopy on the immune system in intra-abdominal sepsis — a review. J Invest Surg. 2008; 21: 330-339. DOI: 10.1080/08941930802438914Karantonis F.F., Nikiteas N., Perrea D., Vlachou A., Giamarellos-Bo-urboulis E.J., Tsigris C., Kostakis A. Evaluation of the effects of laparotomy and laparoscopy on the immune system in intra-abdominal sepsis — a review. J Invest Surg. 2008; 21: 330-339. DOI: 10.1080/08941930802438914Dupont H., Paugam-Burtz C., Muller-Serieys C., Fierobe.L, Chosidow D., Marmuse J.P., Mantz J., Desmonts J.M. Predictive factors of mortality due to polymicrobial peritonitis with Candida isolation in peritoneal fluid in critically ill patients. Arch Surg. 2002; 137: 1341-1346. DOI: 10.1001/archsurg.137.12.1341Dupont H., Paugam-Burtz C., Muller-Serieys C., Fierobe.L, Chosidow D., Marmuse J.P, Mantz J., Desmonts J.M. Predictive factors of mortality due to polymicrobial peritonitis with Candida isolation in peritoneal fluid in critically ill patients. Arch Surg. 2002; 137: 1341-1346. DOI: 10.1001/archsurg.137.12.1341Ja.wad I., Luksic I., Rafnsson S.B. Assessing available information on the burden of sepsis: global estimates of incidence, prevalence and mortality. J Glob Health. 2012; 2 (1): 010404 PMID: 23198133 PMCID: PMC3484761 DOI: 10.7189/jogh.02.010404Jawad I., Luksic I., Rafnsson S.B. Assessing available information on the burden of sepsis: global estimates of incidence, prevalence and mortality. J Glob Health. 2012; 2 (1): 010404 PMID: 23198133 PMCID: PMC3484761 DOI: 10.7189/jogh.02.010404Sartelli M., Abu-Zidan F.M., Ansaloni L, Bala M., Beltran M.A., Biffl W.L., Catena F., Chiara O., Coccolini F., Coimbra R., Demetrashvili Z., Demetriades D., Diaz J.J., Di Saverio S., Fraga G.P., Ghnnam W., Griffiths E.A., Gupta S., Hecker A., Karamarkovic A., Kong V.Y., Kafka.-Ritsch R., Kluger Y., Latifi R., Leppaniemi A., Lee J.G., McFar-lane M., Marwah S., Moore F.A., Ordonez C.A., Pereira G.A., Plaudis H., Shelat V.G., Ulrych J., Zachariah S.K., Zielinski M.D., Garcia M.P., Moore E.E. The role of the open abdomen procedure in managing severe abdominal sepsis: WSES position paper. World J Emerg Surg. 2015; 10: 35. PMID: 26269709 PMCID: PMC4534034 DOI: 10.1186/s13017-015-0032-7Sartelli M., Abu-Zidan F.M., Ansaloni L, Bala M., Beltran M.A., Biffl W.L., Catena F, Chiara O., Coccolini F., Coimbra R., Demetrashvili Z., Demetriades D., Diaz J.J., Di Saverio S., Fraga G.P., Ghnnam W., Griffiths E.A., Gupta S., Hecker A., Karamarkovic A., Kong V.Y., Kafka-Ritsch R., Kluger Y., Latifi R., Leppaniemi A., Lee J.G., McFar-lane M., Marwah S., Moore F.A., Ordonez C.A., Pereira G.A., Plaudis H., Shelat V.G., Ulrych J., Zachariah S.K., Zielinski M.D., Garcia M.P., Moore E.E. The role of the open abdomen procedure in managing severe abdominal sepsis: WSES position paper. World J Emerg Surg. 2015; 10: 35. PMID: 26269709 PMCID: PMC4534034 DOI: 10.1186/s13017-015-0032-7Sartelli M., Viale P, Catena F., Ansaloni L., Moore E., Malangoni M., Moore FA., Velma,hos G., Coimbra R., Ivatury R., Peitzman A., Koike K., Leppa.niemi A., Biffl W., Burlew C.C., Balogh Z.J., Boffard K., Bendinelli C., Gupta S., Kluger Y., Agresta F., Di Saverio S., Wani I., Escalona A., Ordonez C., Frnga G.P, Alves Pereira Jr. G., Bala M., Cui Y., Marwah S., Sakakushev B., Kong V, Naidoo N., Ahmed A., Abbas A., Guercioni G., Vettoretto N., Diaz-Nieto R., Gerych I., Trana C., Faro M.P, Yuan K-Ch.,K. Yuh Yen Kok, Chichom Mefire A., Lee J.G.,Hong S-K., Ghnnam W., Siribumrungwong B.,Sato N.,Murata K., Irahara T., Coccolini F., Segovia Lohse H.A., Verni A., Shoko T. 2013 WSES guidelines for management of intra-abdominal infections. World J Emerg Surg. 2013; 8 (1): 3 DOI: 10.1186/1749-7922-8-3Sartelli M., Viale P., Catena F., Ansaloni L., Moore E., Malangoni M., Moore FA., Velmahos G., Coimbra R., Ivatury R., Peitzman A., Koike K., Leppaniemi A., Biffl W., Burlew C.C., Balogh Z.J., Boffard K., Bendinelli C., Gupta S., Kluger Y., Agresta F., Di Saverio S., Wani I., Escalona A., Ordonez C., Fraga G.P, Alves Pereira Jr. G., Bala M., Cui Y., Marwah S., Sakakushev B., Kong V., Naidoo N., Ahmed A., Abbas A., Guercioni G., Vettoretto N., Diaz-Nieto R., Gerych I., Trana C., Faro M.P., Yuan K-Ch.,K. Yuh Yen Kok, Chichom Mefire A., Lee J.G.,Hong S-K., Ghnnam W., Siribumrungwong B.,Sato N.,Murata K., Irahara T., Coccolini F., Segovia Lohse H.A., Verni A., Shoko T. 2013 WSES guidelines for management of intra-abdominal infections. World J Emerg Surg. 2013; 8 (1): 3 DOI: 10.1186/1749-7922-8-3Montravers P., Gauzit R., Muller C., Marmuse J.P., Fichelle A., Desmonts J.M. Emergence of antibiotic-resistant bacteria in cases of peritonitis after intraabdominal surgery affects the efficacy of empirical antimicrobial therapy. Clin Infect Dis. 1996; 23: 486-494. DOI: 10.1093/clinids/23.3.486Montravers P, Gauzit R., Muller C., Marmuse J.P, Fichelle A., Desmonts J.M. Emergence of antibiotic-resistant bacteria in cases of peritonitis after intraabdominal surgery affects the efficacy of empirical antimicrobial therapy. Clin Infect Dis. 1996; 23: 486-494. DOI: 10.1093/clinids/ 23.3.486Calandra T, Bille J., Schneider R., Mosimann F., Francioli P. Clinical significance of Candida isolated from peritoneum in surgical patients. Lancet. 1989; 2: 1437-1440 DOI: 10.1016/S0140-6736(89)92043-6Calandra T., Bille J., Schneider R., Mosimann F., Francioli P. Clinical significance of Candida isolated from peritoneum in surgical patients. Lancet. 1989; 2: 1437-1440 DOI: 10.1016/S0140-6736 (89)92043-6Hensler T, Hecker H, HeegK., Heidecke C.D., Bartels H., Barthlen W., Wagner H, Siewert J.R., Holzmann B. Distinct mechanisms of immunosuppression as a consequence of major surgery. Infect Immun. 1997; 65 (6): 2283-2291 PMID: 9169765 PMCID: PMC175317Hensler T., Hecker H., HeegK., Heidecke C.D., Bartels H., Barthlen W., Wagner H., Siewert J.R., Holzmann B. Distinct mechanisms of immunosuppression as a consequence of major surgery. Infect Immun. 1997; 65 (6): 2283-2291 PMID: 9169765 PMCID: PMC175317Kimura F, Shimizu H., Yoshidome H., Ohtsuka M., Miyazaki M. Immunosuppression following surgical and traumatic injury. Surg Today. 2010; 40 (9): 793-808. DOI: 10.1007/s00595-010-4323-zKimura F., Shimizu H., Yoshidome H., Ohtsuka M., Miyazaki M. Immunosuppression following surgical and traumatic injury. Surg Today. 2010; 40 (9): 793-808. DOI: 10.1007/s00595-010-4323-zSchrijverI.T., Theroude C., Roger T. Myeloid-Derived Suppressor Cells in Sepsis. Front. Immunol. 2019; 10: 327 PMID: 30873175 PMCID: PMC6400980 DOI: 10.3389/fimmu.2019.00327SchrijverI.T., Theroude C., Roger T. Myeloid-Derived Suppressor Cells in Sepsis. Front. Immunol. 2019; 10: 327 PMID: 30873175 PMCID: PMC6400980 DOI: 10.3389/fimmu.2019.00327Гапонов М.А., Писарев В.М., Тутельян А.В., Лихванцев В.В., Гребенников О.А. Прогностическое значение содержания моноци-тарных миелоидных иммуносупрссорных клеток при сепсисе. Инфекционные болезни. 2015; 13 (4): 72-74GaponovM.A., Pisarev V.M., Tutelyan A.V., Lihvantsev VV, Grebenchi-kov OA. The prognostic value of the content of monocytic myeloid immunosuppressive cells in sepsis.. Infektsionnye bolezni. 2015; 13 (4): 72-74 [In Russ.]Гапонов МА., Хайдуков С.В., Писарев В.М., Гребенников О.А., Гапонов А.М., Тутельян А.В. Субпопуляционная гетерогенность миелоидных иммуносупрессорных клеток у пациентов с септическими состояниями. Российский иммунологический журнал, 2015; 9 (18): 11-14GaponovM.A., Hajdukov S.V, Pisarev V.M., Grebenchikov O.A., Gaponov A.M., Tutelyan A.V. Subpopulation heterogeneity of myeloid immunosuppressive cells in patients with septic conditions. Rossijskij immunologicheskij zhurnal. 2015; 9 (18): 11-14 [In Russ.]PastelJ.J., RosenthalM.D., McClave S.A, MartindaleR.G. (). Tempering the Clinical Effects of Early Myeloid-derived Suppressor Cell Expansion in Severe Sepsis and Septic Shock. American Journal of Respiratory and Critical Care Medicine, 2018; 197 (5): 677-678. DOI: 10.1164/rccm.201708-1701lePatel J.J., Rosenthal M.D., McClave S.A., Martindale R.G. Tempering the Clinical Effects of Early Myeloid-derived Suppressor Cell Expansion in Severe Sepsis and Septic Shock. American Journal of Respiratory and Critical Care Medicine, 2018; 197 (5): 677-678. DOI: 10.1164/rccm.201708-1701leBrudecki L.,Fergu$on DA., McCall C.E.,El Gazzar, M. Myeloid-derived suppressor cells evolve during sepsis and can enhance or attenuate the systemic inflammatory response. Infect. Immun. 2012, 80, 2026-2034 PMID: 22451518 PMCID: PMC3370575 DOI: 10.1128/IAI.00239-12Brudecki L.,Ferguson DA., McCall C.E.,El Gazzar, M. Myeloid-derived suppressor cells evolve during sepsis and can enhance or attenuate the systemic inflammatory response. Infect. Immun. 2012, 80, 2026-2034 PMID: 22451518 PMCID: PMC3370575 DOI: 10.1128/IAI.00239-12Waeckel L., Venet F., Gossez M., Monard C., Rimmele T., Monneret G. Delayed persistence of elevated monocytic MDSC associates with deleterious outcomes in septic shock: a retrospective cohort study. Crit Care. 2020; 24 (1): 132. DOI: 10.1186/s13054-020-02857-yWaeckel L., Venet F., Gossez M., Monard C., Rimmele T., Monneret G. Delayed persistence of elevated monocytic MDSC associates with deleterious outcomes in septic shock: a retrospective cohort study. Crit Care. 2020; 24 (1): 132. DOI: 10.1186/s13054-020-02857-yMathias B., Delmas A.L., Ozrazgat-Baslanti T., Vanzan, E.L., Szpila B.E., MohrA.M., Moore F.A., Brakenridge S.C., BrumbackBA., Molda-wer L.L., Efron P.A., the Sepsis, Critical Illness Research Center Investi-ga.tors. Human Myeloid-derived Suppressor Cells are Associated With Chronic Immune Suppression After Severe Sepsis/Septic Shock. Ann. Surg. 2017; 265: 827-834 PMID: 27163951 PMCID: PMC5102824 DOI: 10.1097/SLA.0000000000001783Mathias B., Delmas A.L., Ozrazgat-Baslanti T., Vanzan, E.L., Szpila B.E., Mohr A.M., Moore F.A., Brakenridge S.C., Brumback B.A., Molda-wer L.L., Efron P.A., the Sepsis, Critical Illness Research Center Investigators. Human Myeloid-derived Suppressor Cells are Associated With Chronic Immune Suppression After Severe Sepsis/Septic Shock. Ann. Surg. 2017; 265: 827-834 PMID: 27163951 PMCID: PMC5102824 DOI: 10.1097/SLA.0000000000001783Albertsmeier M., Prix N.J., Winter H., Bazhin A., Werner J., Angele M.K Monocyte-Dependent Suppression of T-Cell Function in Postoperative Patients and Abdominal Sepsis. Shock. 2017; 48 (6): 651-656. DOI: 10.1097/SHK.0000000000000924Albertsmeier M., Prix N.J., Winter H., Bazhin A., Werner J., Angele M.K. Monocyte-Dependent Suppression of T-Cell Function in Postoperative Patients and Abdominal Sepsis. Shock. 2017; 48 (6): 651-656. DOI: 10.1097/SHK.0000000000000924Pisarev V.M., ChumachenkoA.G., GaponovA.M., Tyurin I.N., Cherpa-kovR., Tutelya.nA.V. Promoter polymorphism in AQP5gene associates with increased survival and decreased numbers of monocytic MDSC in abdominal sepsis (by SEPSIS-3). Shock, 2018. 49: S.1. p.27. https: //journals.lww.com/shockjournal/pages/default.aspxPisarev V.M., ChumachenkoA.G., GaponovA.M., TyurinI.N., Cherpa-kov R., Tutelyan A.V. Promoter polymorphism in AQP5 gene associates with increased survival and decreased numbers of monocytic MDSC in abdominal sepsis (by SEPSIS-3). Shock, 2018. 49: S.1. p.27. https://journals.lww.com/shockjournal/pages/default.aspxDe Waele J., Lipman J., Sakr Y., Marshall J.C., Vanhems P.,Barrera Groba C., Leone M., Vincent J-L. for the EPIC IIInvestigators. Abdominal infections in the intensive care unit: characteristics, treatment and determinants of outcome. BMC Infect Dis. 2014; 14: 420. 2014. DOI: 10.1186/1471-2334-14-420De Waele J., Lipman J., Sakr Y., Marshall J.C., Vanhems P.,Barrera Groba C., Leone M., Vincent J-L. for the EPIC IIInvestigators. Abdominal infections in the intensive care unit: characteristics, treatment and determinants of outcome. BMC Infect Dis. 2014; 14: 420. 2014. DOI: 10.1186/1471-2334-14-420Ja.wa R.S, Quist E, Boyer C.W, Shostrom V.K, Mercer D. W. Mesenteric ischemia-reperfusion injury up-regulates certain CC, CXC, and XC chemokines and results in multi-organ injury in a time-dependent manner. Eur Cytokine Netw. 2013; 24 (4): 148-156. DOI: 10.1684/ecn.2014.0345JawaR.S, QuistE., Boyer C.W, Shostrom V.K, MercerD.W. Mesenteric ischemia-reperfusion injury up-regulates certain CC, CXC, and XC chemokines and results in multi-organ injury in a time-dependent manner. Eur Cytokine Netw. 2013; 24 (4): 148-156. DOI: 10.1684/ecn.2014.0345Rump K., Siffert W., Peters J., Adamzik M. The Transcription Factor NMP4 Binds to the AQP5 Promoter and Is a Novel Transcriptional Regulator of the AQP5 Gene. DNA Cell Biol. 2016; 35 (7): 322-327. DOI: 10.1089/dna.2015.3110Rump K., Siffert W., Peters J., Adamzik M. The Transcription Factor NMP4 Binds to the AQP5 Promoter and Is a Novel Transcriptional Regulator of the AQP5 Gene. DNA Cell Biol. 2016; 35 (7): 322-327. DOI: 10.1089/dna.2015.3110Na.garaj S., Nelson A., Youn J.I., Cheng P., Quiceno D., Gabrilovich D.I. Antigen-specific CD4 (+)T cells regulate function of myeloid-derived suppressor cells in cancer via retrograde MHC class II signaling. Cancer Res. 2012; 72 (4): 928-938. DOI: 10.1158/0008-5472Nagaraj S., Nelson A., Youn J.I., Cheng P., Quiceno D., Gabrilovich D.I. Antigen-specific CD4 (+)T cells regulate function of myeloid-derived suppressor cells in cancer via retrograde MHC class II signaling. Cancer Res. 2012; 72 (4): 928-938. DOI: 10.1158/0008-5472Hou Y., Feng Q., Xu M., Li G-S., Xue-Na Liu X-N., Sheng Z., Zhou H., Ma J, Wei Y., Sun Y-X, Yu Y-Y., Qiu J-H., Shao L-L., Liu X-G., Hou M., Peng J. High-dose dexamethasone corrects impaired myeloid-derived suppressor cell function via Ets1 in immune thrombocytopenia. Blood. 2016; 127 (12): 1587-1597. DOI: 10.1182/blood-2015-10-674531Hou Y., Feng Q., Xu M., Li G-S., Xue-Na Liu X-N., Sheng Z., Zhou H., Ma J., Wei Y., Sun Y-X., Yu Y-Y., Qiu J-H., Shao L-L., Liu X-G., Hou M., Peng J. High-dose dexamethasone corrects impaired myeloid-derived suppressor cell function via Ets1 in immune thrombocytopenia. Blood. 2016; 127 (12): 1587-1597. DOI: 10.1182/blood-2015-10-674531Hanisch E., Brause R., Paetz J., ArltB. Review of a large clinical series: predicting death for patients with abdominal septic shock. J Intensive Care Med. 2011; 26 (1): 27-33 PMID: 21262751 DOI: 10.1177/0885066610384058Hanisch E., Brause R., Paetz J., Arlt B. Review of a large clinical series: predicting death for patients with abdominal septic shock. J Intensive Care Med. 2011; 26 (1): 27-33 PMID: 21262751 DOI: 10.1177/0885066610384058van Ruler O., Kiewiet J.J., Boer K.R,. Lamme B., Gouma D.J., Boermeester M.A., Reitsma J.B. Failure of available scoring systems to predict ongoing infection in patients with abdominal sepsis after their initial emergency laparotomy. BMC Surg. 2011; 11: 38 PMID: 22196238 PMCID: PMC3268736 DOI: 10.1186/1471-2482-11-38ester M.A., Reitsma J.B. Failure of available scoring systems to predict ongoing infection in patients with abdominal sepsis after their initial emergency laparotomy. BMC Surg. 2011; 11: 38 PMID: 22196238 PMCID: PMC3268736 DOI: 10.1186/1471-2482-11-38Chen Y.X., Li C.S. Risk stratification and prognostic performance of the predisposition, infection, response, and organ dysfunction (PIRO)scoring system in septic patients in the emergency department: a cohort study. Crit Care. 2014; 18 (2): R74 PMID: 24739219 PMCID: PMC4056311 DOI: 10.1186/cc13832Chen Y.X., Li C.S. Risk stratification and prognostic performance of the predisposition, infection, response, and organ dysfunction (PIRO)scoring system in septic patients in the emergency department: a cohort study. Crit Care. 2014; 18 (2): R74 PMID: 24739219 PMCID: PMC4056311 DOI: 10.1186/cc13832Pisarev V.M., Chumachenko A.G., Tyurin I.N., Cherpakov R., Tutelyan A.V Prognostic value of a genetic polymorphism of AQP5 in sepsis depends on a source of infection. 39th International Symposium on Intensive Care and Emergency Medicine. Critical Care 2019, 23 (Suppl 2): 82. https: //ccforum.biomedcentral.com/articles/supple-ments/volume-23-supplement-2.PisarevV.M., ChumachenkoA.G., TyurinI.N., CherpakovR., Tutelyan A.V. Prognostic value of a genetic polymorphism of AQP5 in sepsis depends on a source of infection. 39th International Symposium on Intensive Care and Emergency Medicine. Critical Care 2019, 23 (Suppl 2): 82. https: //ccforum.biomedcentral.com/articles/supple-ments/volume-23-supplement-2.

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