Abstract
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.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.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 < 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 < 0.05). Moreover, the levels of CCL23/MPIF-1 and MIF were significantly lower (р < 0.0001) in the RG residents. There was a tendency for decreased levels (р < 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.
Highlights
Цитокины – белки, продуцируемые преимущественно активированными клетками кроветворной и иммунной систем, которые опосредуют межклеточные взаимодействия при кроветворении, воспалении, иммунных процессах и межсистемных коммуникациях, это самая многочисленная и универсальная в функциональном отношении группа гуморальных факторов системы иммунитета
Increased levels of proinflammatory IL-6 and TNFa cytokines, and chemokine CCL20/MIP-3a in blood plasma from Republic of Guinea (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, and 12% had antibodies against hepatitis C virus
Только у одного обследованного жителя Гвинейской Республики в крови был обнаружен HBsAg, у двоих людей (8%) обнаружена ДНК вируса гепатита В, при этом у обследованных лиц обнаружены антитела против вируса гепатита В: у 48% (12 человек) – anti-HBs, у 96% (23 человек) – anti-HBcor
Summary
Арсентьева Н.А.1, Любимова Н.Е.1, Бацунов О.К.1, 2, Семенов А.В.1, 2, Тотолян Арег А.1, 2. 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 < 0,001). Для хемокинов CCL2/MCP-1 и CCL24/ Eotaxin-2 наблюдалась тенденция к снижению их уровня (р < 0,05) в плазме крови жителей Гвинейской Республики. Повышенное содержание провоспалительных цитокинов IL-6, TNFα и хемокина CCL20/MIP-3α в 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. Ключевые слова: цитокины, хемокины, мультиплексный анализ, нормальные значения, здоровые жители, Республика Гвинея
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