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<article article-type="research-article" dtd-version="1.3" 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" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">mimmun</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинская иммунология</journal-title><trans-title-group xml:lang="en"><trans-title>Medical Immunology (Russia)</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1563-0625</issn><issn pub-type="epub">2313-741X</issn><publisher><publisher-name>SPb RAACI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.15789/1563-0625-AOB-2073</article-id><article-id custom-type="elpub" pub-id-type="custom">mimmun-2073</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL ARTICLES</subject></subj-group></article-categories><title-group><article-title>Особенности цитокинового  профиля плазмы крови здоровых жителей Гвинейской Республики</article-title><trans-title-group xml:lang="en"><trans-title>Analysis of blood plasma cytokine profile in healthy residents of the Republic of Guinea</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Арсентьева</surname><given-names>Н. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Arsentieva</surname><given-names>N. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Арсентьева Наталья Александровна - научный сотрудник лаборатории молекулярной  иммунологии</p></bio><bio xml:lang="en"><p>Arsentieva N.A. - PhD (Biology), Senior Research Associate, Laboratory of Molecular Immunology.</p><p>197101, St. Petersburg, Mira str., 14. Phone: 7 (904) 646-57-58</p></bio><email xlink:type="simple">arsentieva_n.a@bk.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Любимова</surname><given-names>Н. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Lyubimova</surname><given-names>N. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Любимова Наталья Евгеньевна  – кандидат биологических наук,  научный сотрудник лаборатории молекулярной  иммунологии.</p><p>Санкт-Петербург</p><p> </p></bio><bio xml:lang="en"><p>Lyubimova Natalia E. - PhD (Biology), Research Associate, Laboratory of Molecular Immunology.</p><p>St. Petersburg</p></bio><email xlink:type="simple">natelu@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бацунов</surname><given-names>О. К.</given-names></name><name name-style="western" xml:lang="en"><surname>Batsunov</surname><given-names>O. K.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Бацунов Олег Константинович  – младший научный сотрудник лаборатории молекулярной  иммунологии С-ПНИИЭМ им. Пастера; старший лаборант кафедры иммунологии Первый С-ПГМУ им. академика И.П.  Павлова.</p><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>Batsunov Oleg K. - Junior Research Associate, Laboratory of Molecular Immunology, St. Petersburg Pasteur Institute; Senior Laboratory Assistant, Department of Immunology, FSPS I. Pavlov MU.</p><p>St. Petersburg</p></bio><email xlink:type="simple">batsunov@gmail.com</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Семёнов</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Semenov</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Семенов Александр Владимирович – доктор биологических наук, заместитель  директора по инновационной работе С-ПНИИЭМ им. Пастера; профессор кафедры иммунологии  Первый С-ПГМУ им. академика И.П.  Павлова.</p><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>Semenov Alexander V. - PhD, MD (Biology), Deputy Director for Innovation, St. Petersburg Pasteur Institute; Professor, Department of Immunology, FSPS I. Pavlov MU.</p><p>St. Petersburg</p></bio><email xlink:type="simple">alexvsemenov@yahoo.com</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Тотолян</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Totolian</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Тотолян Арег Артемович  – доктор медицинских наук, профессор, академик РАН, директор С-ПНИИЭМ им. Пастера; заведующий  кафедрой иммунологии  Первый С-ПГМУ им. академика И.П.  Павлова.</p><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>Totolian Areg A. - PhD, MD (Medicine), Professor, Full Member, Russian Academy of Sciences, Director, St. Petersburg Pasteur Institute; Head, Department of Immunology, FSPS I. Pavlov MU.</p></bio><email xlink:type="simple">totolian@spbraaci.ru</email><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФБУН Санкт-Петербургский научно-исследовательский институт эпидемиологии и микробиологии имени Пастера</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Saint-Petersburg Pasteur Institute</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФБУН Санкт-Петербургский научно-исследовательский институт эпидемиологии и микробиологии имени Пастера; ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФ</institution><country>Россия</country></aff><aff xml:lang="en"><institution>St. Petersburg Pasteur Institute; First St. Petersburg State I. Pavlov Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>06</day><month>08</month><year>2020</year></pub-date><volume>22</volume><issue>4</issue><fpage>765</fpage><lpage>778</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Арсентьева Н.А., Любимова Н.Е., Бацунов О.К., Семёнов А.В., Тотолян А.А., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Арсентьева Н.А., Любимова Н.Е., Бацунов О.К., Семёнов А.В., Тотолян А.А.</copyright-holder><copyright-holder xml:lang="en">Arsentieva N.A., Lyubimova N.E., Batsunov O.K., Semenov A.V., Totolian A.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.mimmun.ru/mimmun/article/view/2073">https://www.mimmun.ru/mimmun/article/view/2073</self-uri><abstract><p>Система цитокинов – большая группа факторов, продуцируемых клетками иммунной системы  и участвующих в патогенезе большинства заболеваний человека. Для оценки значимости изменений цитокинов/хемокинов при патологических состояниях необходимо знать физиологический диапазон этих молекул у здоровых людей.  В литературе подавляющее большинство исследований по оценке различных цитокинов/хемокинов в плазме крови практически здоровых лиц  проводили на популяции жителей Западной Европы и Северной Америки. Известны межпопуляционные различия в синтезе определенных цитокинов у разных расовых и национальных групп.  Представлены лишь единичные сведения о нормальном уровне  некоторых цитокинов в плазме крови здоровых жителей Африканского  континента.  Целью данной  работы было  определение особенностей цитокинового профиля плазмы крови практически здоровых жителей Гвинейской Республики и установление нормальных значений цитокинов. Было  обследовано 24 практически здоровых жителя Гвинейской Республики в возрасте от 25 до 64 лет и 23 жителя Санкт-Петербурга в возрасте от 25 до 61 года. Определяли концентрации 40 цитокинов/хемокинов. Исследование проводили с помощью мультиплексного  анализа с применением технологии xMAP  (Luminex, США) с использованием наборов с магнитными частицами Bio-Plex Pro Human Chemokine Assay (Bio-Rad, США). В плазме крови жителей Гвинейской Республики были достоверно повышены концентрации следующих цитокинов и хемокинов: IFNγ, IL-2, IL-4, IL-6, IL-10, TNFα, CCL1/I-309, CCL3/MIP-1α, CCL7/MCP-3, CCL17/TARC, CCL19/MIP-3β,  CCL20/MIP-3α,  CCL21/6Ckine, CXCL2/Gro-β,  CXCL5/ENA-78, CXCL6/GCP-2, CXCL9/MIG, CX3CL1/Fractalkine (р &lt; 0,001).  Для  хемокинов CCL8/MCP-2, CCL22/MDC, CXCL1/ Gro-α и CXCL12/SDF-1α+β наблюдалась тенденция к повышению их концентрации по сравнению с жителями Санкт-Петербурга (р &lt; 0,05). В то же время уровни CCL23/MPIF-1 и MIF были достоверно ниже  (р &lt; 0,0001)  в группе  жителей Гвинейской Республики. Для хемокинов CCL2/MCP-1 и CCL24/ Eotaxin-2 наблюдалась тенденция к снижению их уровня (р &lt; 0,05) в плазме крови жителей Гвинейской Республики. В обследованных группах не обнаружено различий в содержании цитокинов/хемокинов: GM-CSF, IL-1β, IL-16, CCL11/Eotaxin, CCL13/MCP-4, CCL15/Leukotactin-1, CCL25/TECK, CCL26/Eotaxin-3, CCL27/CTACK, CXCL8/IL-8, CXCL10/IP-10, CXCL11/I-TAC, CXCL13/BCA и CXCL16/SCYB16.</p><p>В настоящем исследовании впервые определены границы нормы содержания широкого спектра цитокинов/хемокинов в плазме крови у жителей Африканского региона. Выявлены межпопуляционные различия, в том числе  среди  конститутивных хемокинов. Различные уровни конститутивных хемокинов  CCL19/MIP-3β­ и СCL21/6Ckine – лигандов рецептора CCR7 – в двух популяциях косвенно могут  свидетельствовать о физиологических особенностях созревания Т-клеток.  Повышенный уровень в плазме крови гвинейцев лигандов рецептора CXCR2 – CXCL2/Gro-β, CXCL5/ENA-78 и CXCL6/GCP-2 – может  быть связан с тем,  что эти хемокины также  являются  лигандами для атипичного хемокинового рецептора DARC (Duffy  Antigen  Receptor for Chemokines), обеспечивающего нейтрализацию хемокинов из кровообращения, а 95% жителей Западной Африки имеют  мутации в гене  DARC и не экспрессируют этот  рецептор. Повышенное содержание провоспалительных цитокинов IL-6, TNFα и хемокина CCL20/MIP-3α­в плазме жителей Гвинейской Республики, возможно, свидетельствует о воспалительных процессах в печени, так как среди обследованных нами гвинейцев у 100% людей  были  выявлены антитела против вируса  гепатита А, у 48% – антитела против вируса гепатита В (анти-HBs) и у 12% – антитела против вируса  гепатита С. В целом  различия в содержании цитокинов/хемокинов могут быть  связаны с разной средой  обитания, циркуляцией инфекционных заболеваний, содержанием микробиоты кишечника, кожи  и слизистых, а также  генетическими различиями.</p></abstract><trans-abstract xml:lang="en"><p>The cytokine system is a large group of humoral factors  produced by immune cells and involved in the  pathogenesis of most  human diseases.  To assess the  significance of changes  in cytokines/chemokines under  pathological conditions, appropriate reference values are required for healthy  people.  As known  from existing literature, most studies of various cytokine/chemokine concentrations in blood plasma were performed in healthy  subjects from Western Europe and North America.  Certain inter-population differences are known, with  respect  to production of distinct cytokines in different  racial  and  national groups.  Only  single studies concern normal levels of distinct cytokines in blood  plasma  of healthy  African  residents. The purpose  of this study was to determine the blood plasma cytokine profile in healthy  residents of the Republic of Guinea (RG), and to establish normal cytokine values.</p><p>We have  examined 24  healthy  RG  residents and  23  residents of St.  Petersburg. Concentrations  of 40 cytokines/chemokines were determined in blood plasma.  The study was performed using multiplex analysis by xMAP technology.</p><p>The  following  cytokine/chemokine levels  were  significantly   increased in  the  blood  plasma  of the  RG residents: IFNγ, IL-2, IL-4, IL-6, IL-10, TNFα, CCL1/I-309, CCL3/MIP-1α, CCL7/MCP-3, CCL17/ TARC, CCL19/MIP-3β,  CCL20/MIP-3α,  CCL21/6Ckine, CXCL2/Gro-β,  CXCL5/ENA-78, CXCL6/ GCP-2, CXCL9/MiG, CX3CL1/Fractalkine (р &lt; 0.001).  For  the  CCL8/MCP-2, CCL22/MDC, CXCL1/ Gro-α and CXCL12/SDF-1α+β chemokines a trend for increased concentration was revealed, in comparison with residents of St. Petersburg (р &lt; 0.05). Moreover, the levels of CCL23/MPIF-1 and MIF were significantly lower (р &lt; 0.0001) in the RG residents. There was a tendency for decreased levels (р &lt; 0.05) for CCL2/MCP-1 and CCL24/Eotaxin-2 chemokines in blood plasma taken from RG residents. There were no differences in levels of cytokines/chemokines for the studied  groups: GM-CSF, IL-1β, IL-16, CCL11/Eotaxin, CCL13/MCP-4, CCL15/Leukotactin-1, CCL25/TECK, CCL26/Eotaxin-3, CCL27/CTACK, CXCL8/IL-8, CXCL10/IP-10, CXCL11/I-TAC, CXCL13/BCA, and  CXCL16/SCYB16. Hence, this study  has presented for the  first time the normal limits for a wide range of cytokines/chemokines in blood plasma  of the African inhabitants. Interpopulation differences were found, including those  for constitutive chemokines. Different levels of CCL19/ MIP-3β and CCL21/6Ckine chemokines (the CCR7 receptor ligands) for the two populations may indirectly indicate the physiological features of T-cell maturation. Increased levels of CXCR2 receptor ligands in the blood plasma  of Guineans, i.e.,  CXCL2/Gro-β, CXCL5/ENA-78 and  CXCL6/GCP-2, may be due  to additional function of these chemokines as ligands for atypical DARC chemokine receptor, which neutralizes chemokines from the blood flow, whereas 95% of West Africans have mutations in the DARC gene and do not express this receptor. Increased levels of proinflammatory IL-6  and TNFα cytokines, and chemokine CCL20/MIP-3α in blood plasma  from RG  residents may suggest inflammatory processes  in the liver, since 100% of the examined Guineans had antibodies against the hepatitis A virus, 48% had antibodies to hepatitis B virus (anti-HBs), and 12% had antibodies against hepatitis C virus. In summary, the differences in cytokine/chemokine level may be related  to specific environment, circulation of infectious diseases, composition of intestinal, skin and mucosal microbiota, as well as distinct genetic  features.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>цитокины</kwd><kwd>хемокины</kwd><kwd>мультиплексный анализ</kwd><kwd>нормальные значения</kwd><kwd>здоровые жители</kwd><kwd>Республика</kwd></kwd-group><kwd-group xml:lang="en"><kwd>cytokines</kwd><kwd>chemokines</kwd><kwd>multiplex analysis</kwd><kwd>normal values</kwd><kwd>healthy residents</kwd><kwd>Republic of Guinea</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Арсентьева Н.А., Тотолян А.А. Методические сложности при определении содержания некоторых цитокинов в периферической крови практически здоровых лиц // Медицинская иммунология, 2018. Т. 20, № 5. 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