mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2019-4-725-736mimmun-1882Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESКОНЦЕНТРАЦИЯ ПРОТИВОВОСПАЛИТЕЛЬНЫХ ЦИТОКИНОВ В СУПЕРНАТАНТАХ КУЛЬТУР ЦЕЛЬНОЙ КРОВИ У ДЕТЕЙ С ЮВЕНИЛЬНЫМ ИДИОПАТИЧЕСКИМ АРТРИТОМСONCENTRATION OF ANTI-INFLAMATORY CYTOKINES IN CELL CULTURE SUPERNATANTS IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITISКриволаповаИ. М.KrivolapovaI. M.

биолог клинико-диагностической лаборатории; младший научный сотрудник лаборатории иммунологии воспаления

620149, Россия, г. Екатеринбург, ул. С. Дерябиной, 32

Тел.: 8 (343) 231-91-28

Research Biologist, Laboratory of Clinical Diagnostics; Junior Research Associate, Laboratory of Immunology of Inflammation

620149, Russian Federation, Ekaterinburg, S. Deryabina str., 32

Phone: 7 (343) 231-91-28

krivolapovaim@mis66.ruПашнинаИ. А.PashninaI. A.

д.б.н., заведующая клинико-диагностической лабораторией; старший научный сотрудник лаборатории иммунологии воспаления 

Екатеринбург

PhD, MD (Biology), Head, Laboratory of Clinical Diagnostics; Senior Research Associate, Laboratory of Immunology of Inflammation

Ekaterinburg

ЧерешневВ. А.ChereshnevV. A.

д.м.н., профессор, академик РАН, главный научный сотрудник

Екатеринбург

PhD, MD (Medicine), Professor, Full Member, Russian Academy of Sciences, Main Research Associate

Ekaterinburg

ГБУЗ СО «Областная детская клиническая больница № 1», ФГБУН «Институт иммунологии и физиологии» Уральского отделения Российской академии наукРоссияRegional Children’s Clinical Hospital No. 1, Institute of Immunology and Physiology, Ural Branch, Russian Academy of ScienceRussian FederationГБУЗ СО «Областная детская клиническая больница № 1», ФГБУН «Институт иммунологии и физиологии» Уральского отделения Российской академии наукРоссияRegional Children’s Clinical Hospital No. 1; Institute of Immunology and Physiology, Ural Branch, Russian Academy of ScienceRussian FederationФГБУН «Институт иммунологии и физиологии» Уральского отделения Российской академии наукРоссияInstitute of Immunology and Physiology, Ural Branch, Russian Academy of SciencesRussian Federation201928102019214препринт725736Copyright © Криволапова И.М., Пашнина И.А., Черешнев В.А., 20192019Криволапова И.М., Пашнина И.А., Черешнев В.А.Krivolapova I.M., Pashnina I.A., Chereshnev V.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/1882

Ювенильный идиопатический артрит представляет собой гетерогенную группу заболеваний, преимущественно аутоиммунной или аутовоспалительной природы, основным проявлением которых является хроническое течение воспалительного процесса суставов у детей. В основе патогенеза разных форм ювенильного артрита, вероятно, лежат разные механизмы. Однако при всех вариантах ювенильного артрита развивается длительный дисбаланс между продукцией про- и противовоспалительных цитокинов в сторону преобладания первых.Цель исследования – определение уровня спонтанной и стимулированной продукции противоспалительных цитокинов в супернатантах культур цельной крови у детей с ювенильным идиопатическим артритом.Обследованы дети и подростки 2-17 лет с различными вариантами ювенильного идиопатического артрита (n = 99) и условно здоровые дети (контроль, n = 31). Спонтанную и фитогемагглютинин-стимулированную концентрацию IL-1rа, IL-4, IL-10, TGF-β в супернатантах клеточных культур исследовали методом ИФА.Различий по спонтанной и митоген-стимулированной секреции исследованных цитокинов между пациентами с различными вариантами ювенильного артрита не выявлено. В объединенной группе больных с ювенильным идиопатическим артритом спонтанная выработка IL-1rа, IL-4 и IL-10 клетками крови оставалась на уровне контрольной. У пациентов медианное значение спонтанной концентрации TGF-β было нулевым, тогда как клетки крови здоровых детей обладали значимо более высоким потенциалом продукции TGF-β. После инкубации клеток периферической крови с фитогемагглютинином синтез IL-4 и IL-10 у больных не отличался от контрольного уровня, а интенсивность выработки IL-1rа и ТGF-β была достоверно ниже, чем у здоровых детей.Более низкая по сравнению с контролем спонтанная и/или стимулированная продукция клетками крови IL-1rа и ТGF-β у детей с ювенильным идиопатическим артритом по сравнению с контрольной группой отражает патогенетическую значимость данных цитокинов при этом заболевании. Стимуляция клеток способна выявить скрытый дефицит синтеза цитокинов, не проявляющийся при определении его концентрации в сыворотке крови или супернатантах спонтанных клеточных культур. 

Juvenile idiopathic arthritis is a chronic inflammatory disease of the joints in children, mainly of autoimmune or auto-inflammatory nature. It is a heterogeneous group, which includes different subtypes of the disease. Different mechanisms may play role in the pathogenesis of distinct subtypes of juvenile arthritis. However, a long-term imbalance of pro- and anti-inflammatory cytokines is important for all subtypes of disease. The aim of the present study was to determine spontaneous and stimulated anti-inflammatory cytokines production by peripheral blood cells from the children with juvenile idiopathic arthritis. Patients of 2 to 17 years old with different subtypes of juvenile idiopathic arthritis (n = 99) and healthy children without signs of autoimmune diseases (control, n = 31) were examined. Spontaneous and phytohemagglutinin-stimulated concentrations of IL-1ra, IL-4, IL-10, TGF-β in supernatants of whole-blood cultures were determined by ELISA. Differences in the spontaneous and mitogen-stimulated secretion of the cytokines in patients with different subtypes of juvenile arthritis have not been revealed. The spontaneous IL-1ra, IL-4 and IL-10 production by blood cells in the common group of patients with juvenile idiopathic arthritis was similar to the controls. The median value of spontaneous TGF-β concentration in the patients was below the detection level, whereas blood cells of healthy children had a higher potential of spontaneous TGF-β production. IL-4 and IL-10 production after incubation of peripheral blood cells with phytohemagglutinin in patients and in the control group did not differ from the controls, while IL-1ra and TGF-β synthesis was significantly lower than in healthy children.The spontaneous and/or stimulated production of IL-1ra, TGF-β by blood cells in children with juvenile idiopathic arthritis reflects the pathogenic significance of these cytokines in disease. Stimulation of cells can reveal a latent deficiency in the synthesis of cytokines, which is not evident when determining its concentration in serum or supernatants of spontaneous whole-blood cultures.

стимуляция in vitroювенильные артритыдетикультуры клетокцитокинывоспалениеin vitro stimulationjuvenile arthritischildrencells culturecytokinesinflammationРабота выполнена в рамках госзадания ИИФ УрО РАН (регистрационный номер НИОКТР № АААА-А18-118020590108-7).ReferencesАвдеева А.С., Кусевич Д.А. Роль лабораторных биомаркеров в прогнозировании эффективности терапии ритуксимабом при ревматоидном артрите (новые данные) // Научно-практическая ревматология, 2017. T. 55, № 3. C. 295-303.Avdeeva A.S., Kusevich D.A. The role of laboratory biomarkers in predicting the efficiency of rituximab therapy for rheumatoid arthritis: new evidence. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice, 2017, Vol. 55, no. 3, pp. 295-303. (In Russ.)Алексеева Е.И. Ювенильный идиопатический артрит: клиническая картина, диагностика, лечение // Вопросы современной педиатрии, 2015. T. 14, № 1. C. 78-94.Alekseeva E.I. Juvenile idiopathic arthritis: Clinical picture, Diagnosis, Treatment. Voprosy sovremennoy pediatrii = Current Pediatrics, 2015, Vol. 14, no. 1, pp. 78-94. (In Russ.)Алексеева Е.И., Бзарова Т.М. Ювенильный ревматоидный артрит. В кн.: Педиатрия. Национальное руководство. Краткое издание / под ред. А.А. Баранова. М.: ГЭОТАР-Медиа, 2014. 768 сAlekseeva E.I., Bzarova T.M. Juvenile idiopathic arthritis. In the book: Pediatrics. National guidance. Short edition. Ed. A.A. Baranov. Moscow: GEOTAR-Media, 2014. 768 p.Герцев А.В., Закревский Ю.Н. Характеристика нейропептидно-цитокинового звена иммунитета у больных с полиморбидной сердечно-сосудистой патологией, протекающей на фоне тревожно-депрессивных расстройств // Медицинская иммунология, 2018. Т. 20, № 2. С. 277-284. doi: 10.15789/1563-0625-2018-2-277-284.Gertsev A.V., Zakrevsky Yu.N. Characteristics of neuropeptide-cytokine immunity links in patients with combined cardiovascular pathology, proceeding with anxiety/depression disorder. Meditsinskaya immunologiya = Medical Immunology (Russia), 2018, Vol. 20, no. 2, pp. 277-284. (In Russ.) doi: 10.15789/1563-0625-2018-2-277-284.Демьянов А.В., Котов А.Ю., Симбирцев А.С. Диагностическая ценность исследования уровней цитокинов в клинической практике // Цитокины и воспаление, 2003. T. 2, № 3. C. 20-35.Gertsev A.V., Zakrevsky Yu.N. Characteristics of neuropeptide-cytokine immunity links in patients with combined cardiovascular pathology, proceeding with anxiety/depression disorder. Meditsinskaya immunologiya = Medical Immunology (Russia), 2018, Vol. 20, no. 2, pp. 277-284. (In Russ.) doi: 10.15789/1563-0625-2018-2-277-284.Каледа М.И., Никишина И.П., Шаповаленко А.Н., Костарева О.М., Федоров Е.С. Феномен нейтропении на фоне терапии тоцилизумабом у пациентов с ювенильным идиопатическим артритом // Научно-практическая ревматология, 2017. Т. 55, № 6. С. 662-667.Demyanov A.V., Kotov A. Yu., Simbirtsev A.S. Diagnostic value of cytokine studies in clinical practice. Citokiny i vospalenie = Cytokines and Inflammation, 2003, Vol. 2, no. 3, pp. 20-35. (In Russ.)Кетлинский С.А., Симбирцев А.С. Цитокины. СПб.: Фолиант, 2008. 552 с.Demyanov A.V., Kotov A. Yu., Simbirtsev A.S. Diagnostic value of cytokine studies in clinical practice. Citokiny i vospalenie = Cytokines and Inflammation, 2003, Vol. 2, no. 3, pp. 20-35. (In Russ.)Кожевников А.Н., Поздеева Н.А., Конев М.А., Селизов В.В., Прокопович Е.В., Никитин М.С., Москаленко А.В., Афоничев К.А. Ювенильный артрит: клинико-инструментальная картина и дифференциальная диагностика // Ортопедия, травматология и восстановительная хирургия детского возраста, 2014. Т. 2, № 4. С. 66-73.Kaleda M.I., Nikishina I.P., Shapovalenko A.N., Kostareva O.M., Fedorov E.S. The phenomenon of neutropenia during tocilizumab therapy in patients with juvenile idiopathic arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice, 2017, Vol. 55, no. 6, рр. 662-667. (In Russ.)Коненков В.И., Ракова И.Г., Авдошина В.В., Гельфгат Е.Л. Комплексная оценка уровня спонтанной продукции цитокинов в культуре мононуклеарых клеток периферической крови здорового человека // Цитокины и воспаление, 2005. № 2. C. 33-37Kaleda M.I., Nikishina I.P., Shapovalenko A.N., Kostareva O.M., Fedorov E.S. The phenomenon of neutropenia during tocilizumab therapy in patients with juvenile idiopathic arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice, 2017, Vol. 55, no. 6, рр. 662-667. (In Russ.)Костик М.М. Применение анакинры у пациентов с криопиринассоциированными периодическими синдромами и другими аутовоспалительными заболеваниями // Вопросы современной педиатрии, 2016.Ketlinsky S.A., Simbirtsev A.S. Cytokines. St. Petersburg: Foliant, 2008. 552 p.Т. 15, № 6. С. 576-583.Ketlinsky S.A., Simbirtsev A.S. Cytokines. St. Petersburg: Foliant, 2008. 552 p.Никишина И.П., Каледа М.И. Современная фармакотерапия системного ювенильного артрита // Научно-практическая ревматология, 2015. Т. 53, № 1. С. 84-93.Kozhevnikov A.N., Pozdeeva N.A., Konev M.A., Selizov V.V., Prokopovich E.V., Nikitin M.S., Moskalenko A.V., Afonichev K.A. Juvenile arthritis: clinical manifestations and differential diagnosis. Ortopediya, travmatologiya i vosstanovitelnaya khirurgiya detskogo vozrasta = Pediatric Traumatology, Orthopaedics and Reconstructive Surgery, 2014, Vol. 2, no. 4, pp. 66-73. (In Russ.)Пашнина И.А., Криволапова И.М., Козлова Е.С., Скоробогатова О.В., Тузанкина И.А., Черешнев В.А. Аутоантитела при ювенильных артритах у детей // Российский иммунологический журнал, 2013. Т. 7 (16), № 4. С. 437-444.Kozhevnikov A.N., Pozdeeva N.A., Konev M.A., Selizov V.V., Prokopovich E.V., Nikitin M.S., Moskalenko A.V., Afonichev K.A. Juvenile arthritis: clinical manifestations and differential diagnosis. Ortopediya, travmatologiya i vosstanovitelnaya khirurgiya detskogo vozrasta = Pediatric Traumatology, Orthopaedics and Reconstructive Surgery, 2014, Vol. 2, no. 4, pp. 66-73. (In Russ.)Полушина Л.Г., Светлакова Е.Н., Семенцова Е.А., Мандра Ю.В., Базарный В.В. Клинико-патогенетическое значение некоторых цитокинов при пародонтите // Медицинская иммунология, 2017. Т. 19, № 6. С. 803-806. doi: 10.15789/1563-0625-2017-6-803-806.Konenkov V.I., Rakova I.G., Avdoshina V.V., Gelfgat E.L. Complex evaluation of spontaneous cytokines production in the culture of peripheral blood mononuclear cells of healthy person. Citokiny i vospalenie = Cytokines and Inflammation, 2005, no. 2, pp. 33-37. (In Russ.)Симбирцев А.С. Цитокины в патогенезе инфекционных и неинфекционных заболеваний человека // Медицинский академический журнал, 2013. T. 13, № 3. C. 18-41.Konenkov V.I., Rakova I.G., Avdoshina V.V., Gelfgat E.L. Complex evaluation of spontaneous cytokines production in the culture of peripheral blood mononuclear cells of healthy person. Citokiny i vospalenie = Cytokines and Inflammation, 2005, no. 2, pp. 33-37. (In Russ.)Чернышева О.Е., Конюшевская А.А., Вайзер Н.В., Балычевцева И.В. Ювенильный артрит: терминология, классификация, диагностические критерии, этиология, патогенез, современные аспекты (обзор литературы) // Травма, 2017. Т. 18. № 4. С. 16-24.Kostik M.M. Use of anakinra in patients with cryopyrin-associated periodic syndromes and other autoinflammatory diseases. Voprosy sovremennoy pediatrii = Current Pediatrics, 2016, Vol. 15, no. 6, pp. 576- 583. (In Russ.)Aggarwal А., Mishra R. Cytokine production by peripheral blood mononuclear cells patients with juvenile idiopathic arthritis. Indian Pediatrics., 2002, no. 39, pp. 739-742.Kostik M.M. Use of anakinra in patients with cryopyrin-associated periodic syndromes and other autoinflammatory diseases. Voprosy sovremennoy pediatrii = Current Pediatrics, 2016, Vol. 15, no. 6, pp. 576- 583. (In Russ.)Barut K., Adrovic A., Şahin S., Kasapçopur O. Juvenile idiopathic arthritis. Balkan Med. J., 2017, Vol. 34, no. 2, pp. 90-101.Nikishina I.P., Kaleda M.I. Current pharmacotherapy for systemic juvenile arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice, 2015, Vol. 53, no. 1, pp. 84-93. (In Russ.)Brescia A.C., Simonds M.M., Sullivan K.E., Rose C.D. Secretion of pro-inflammatory cytokines and chemokines and loss of regulatory signals by fibroblast-like synoviocytes in juvenile idiopathic arthritis. Proteomics Clin. Appl., 2017, Vol. 11, no. 5-6.Nikishina I.P., Kaleda M.I. Current pharmacotherapy for systemic juvenile arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice, 2015, Vol. 53, no. 1, pp. 84-93. (In Russ.)Chyuan I.T., Chen J.Y. Role of interleukin- (IL-) 17 in the pathogenesis and targeted therapies in spondyloarthropathies. Mediators Inflamm., 2018, 2403935, 8 p. doi: 10.1155/2018/2403935.Pashnina I.A., Krivolapova I.M., Kozlova E.S., Skorobogatova O.V., Tuzankina I.A., Chereshnev V.A. Autoantibodies in children with juvenile arthritis. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2013, Vol. 7 (16), no. 4, pp. 437-444. (In Russ.)de Jager. Cytokines in juvenile idiopathic arthritis. Ann. Rheum. Dis., 2017, Vol. 76, no. 2, pp. 16-17.Pashnina I.A., Krivolapova I.M., Kozlova E.S., Skorobogatova O.V., Tuzankina I.A., Chereshnev V.A. Autoantibodies in children with juvenile arthritis. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2013, Vol. 7 (16), no. 4, pp. 437-444. (In Russ.)de Jager, Hoppenreijs E.P.A.H., Wulffraat N.M., Wedderburn L.R, Kuis W., Prakken B.J. Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: a cross-sectional study. Ann. Rheum. Dis., 2007, no. 66, pp. 589-598.Polushina L.G., Svetlakova E.N., Sementsova E.A., Mandra Yu.V., Bazarny V.V. Clinico-pathogenetic value of some cytokines in periodontitis. Meditsinskaya immunologiya = Medical Immunology (Russia), 2017, Vol. 19, no. 6, pp. 803-806. (In Russ.) doi: 10.15789/1563-0625-2017-6-803-806.Dong C., Fu T., Ji J., Li Z., Gu Z. The role of interleukin-4 in rheumatic diseases. Clin. Exp. Pharmacol. Physiol., 2018, Vol. 45, no. 8, pp. 747-754.Polushina L.G., Svetlakova E.N., Sementsova E.A., Mandra Yu.V., Bazarny V.V. Clinico-pathogenetic value of some cytokines in periodontitis. Meditsinskaya immunologiya = Medical Immunology (Russia), 2017, Vol. 19, no. 6, pp. 803-806. (In Russ.) doi: 10.15789/1563-0625-2017-6-803-806.Guo L., Lu M.P., Dong G.J., Teng L.P., Xu Y.P., Zou L.X., Zheng Q. Clinical and laboratory features of macrophage activation syndrome. Zhongguo Dang Dai Er Ke Za Zhi, 2017, Vol. 19, no. 2, pp. 188-192.Simbirtsev A.S. Cytokines in the pathogenesis of infectious and noninfectious human diseases. Meditsinskiy akademicheskiy zhurnal = Medical Academic Journal, 2013, Vol. 13, no. 3, pp. 18-41. (In Russ.)Guo L., Lu M.P., Tang Y.M., Teng L.P., Xu Y.P., Zou L.X., Zheng R.J., Zheng Q. Serum cytokine levels in children with newly diagnosed active systemic juvenile idiopathic arthritis. Zhongguo Dang Dai Er Ke Za Zhi, 2014, Vol. 16, no. 12, pp. 1241-1244.Simbirtsev A.S. Cytokines in the pathogenesis of infectious and noninfectious human diseases. Meditsinskiy akademicheskiy zhurnal = Medical Academic Journal, 2013, Vol. 13, no. 3, pp. 18-41. (In Russ.)Gohar F., Kessel Ch., Lavric M., Holzinger D., Foell D. Review of biomarkers in systemic juvenile idiopathic arthritis: helpful tools or just playing tricks? Arthritis Res. Ther., 2016, Vol. 18, p. 163.Chernyshova O.E., Konyshevskaya A.A., Vaizer N.V., Balychevtseva I.V. Juvenile arthritis: terminology, classification, diagnostic criteria, etiology, pathogenesis, modern aspects (review of the literature). Travma = Trauma, 2017, Vol. 18, no. 4, pp. 16-24. (In Russ.)Harsini S., Ziaee V., Maddah M., Rezaei A., Sadr M., Zoghi S., Moradinejad M.H., Tahghighi F., Aghighi Y., Rezaei N. Interleukin 10 and transforming growth factor beta 1 gene polymorphisms in juvenile idiopathic arthritis. Bratisl. Med. J., 2016, Vol. 117, no. 5, рр. 258-262.Chernyshova O.E., Konyshevskaya A.A., Vaizer N.V., Balychevtseva I.V. Juvenile arthritis: terminology, classification, diagnostic criteria, etiology, pathogenesis, modern aspects (review of the literature). Travma = Trauma, 2017, Vol. 18, no. 4, pp. 16-24. (In Russ.)Heney D., Whicher T.J. Factors affecting the measurement of cytokines in biological fluids: implications for their clinical measurement. Ann. Clin. Biochem., 1995, no. 32, pp. 358-368.Aggarwal А., Mishra R. Cytokine production by peripheral blood mononuclear cells patients with juvenile idiopathic arthritis. Indian Pediatrics., 2002, no. 39, pp. 739-742.Hong K.H., Cho M.L., Min S.Y., Shin Y.J., Yoo S.A., Choi J.J., Kim W.U., Song S.W., Chо C.S. Effect of interleukin-4 on vascular endothelial growth factor production in rheumatoid synovial fibroblasts. Clin. Exp. Immunol., 2007, Vol. 147, no. 3, pp. 573-579.Aggarwal А., Mishra R. Cytokine production by peripheral blood mononuclear cells patients with juvenile idiopathic arthritis. Indian Pediatrics., 2002, no. 39, pp. 739-742.Horai R., Saijo S., Tanioka H., Nakae S., Sudo K., Okahara A., Ikuse T., Asano M., Iwakura Y. Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice. J. Exp. Med., 2000, Vol. 191, no. 2, рр. 313-320.Barut K., Adrovic A., Şahin S., Kasapçopur O. Juvenile idiopathic arthritis. Balkan Med. J., 2017, Vol. 34, no. 2, pp. 90-101.Huang J.L., Kuo M.L., Hung I.J., Wu C.J., Ou L.H., Cheng J.H. Lowered IL-4-producing T cells and decreased IL-4 secretion in peripheral blood from subjects with juvenile rheumatoid arthritis. Chang Gung Med. J., 2001, Vol. 24, no. 2, pp. 77-83.Barut K., Adrovic A., Şahin S., Kasapçopur O. Juvenile idiopathic arthritis. Balkan Med. J., 2017, Vol. 34, no. 2, pp. 90-101.Johdi N.A., Mazlan L., Sagap I., Jamal R. Profiling of cytokines, chemokines and other soluble proteins as a potential biomarker in colorectal cancer and polyps. Cytokine, 2017, no. 99, рр. 35-42.Brescia A.C., Simonds M.M., Sullivan K.E., Rose C.D. Secretion of pro-inflammatory cytokines and chemokines and loss of regulatory signals by fibroblast-like synoviocytes in juvenile idiopathic arthritis. Proteomics Clin. Appl., 2017, Vol. 11, no. 5-6.Kawasumi H., Gono T., Tanaka E., Kaneko H., Kawaguchi Y., Yamanaka H. Clinical characteristics and cytokine profiles of organizing pneumonia in patients with rheumatoid arthritis treated with or without biologics. J. Rheumatol., 2014, Vol. 43, no. 4, pp. 738-744.Brescia A.C., Simonds M.M., Sullivan K.E., Rose C.D. Secretion of pro-inflammatory cytokines and chemokines and loss of regulatory signals by fibroblast-like synoviocytes in juvenile idiopathic arthritis. Proteomics Clin. Appl., 2017, Vol. 11, no. 5-6.Kutukculer N., Caglayan S., Aydogdu F. Study of pro-inflammatory (TNF-alpha, IL-1alpha, IL-6) and T-cellderived (IL-2, IL-4) cytokines in plasma and synovial fluid of patients with juvenile chronic arthritis: correlations with clinical and laboratory parameters. Clin. Rheumatol., 1998, Vol. 17, no. 4, pp. 288-292.Chyuan I.T., Chen J.Y. Role of interleukin- (IL-) 17 in the pathogenesis and targeted therapies in spondyloarthropathies. Mediators Inflamm., 2018, 2403935, 8 p. doi: 10.1155/2018/2403935.Lee C.K., Lee E.Y., Chung S.M., Mun S.H., Yoo B., Moon H.B. Effects of disease-modifying antirheumatic drugs and antiinflammatory cytokines on human osteoclastogenesis through interaction with receptor activator of nuclear factor kappa B, osteoprotegerin, and receptor activator of nuclear factor kappa B ligand. Arthritis Rheum., 2004, Vol. 50, no. 12, pp. 3831-3843.Chyuan I.T., Chen J.Y. Role of interleukin- (IL-) 17 in the pathogenesis and targeted therapies in spondyloarthropathies. Mediators Inflamm., 2018, 2403935, 8 p. doi: 10.1155/2018/2403935.Lijiao J., Meiping L.U., Li G., Jianqiang W.U., Lixia Z., Yiping X.U. Serum levels of Th1/Th2 cytokines in children with non-systemic juvenile idiopathic arthritis. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2016, Vol. 45, no. 3, pp. 281-286.de Jager. Cytokines in juvenile idiopathic arthritis. Ann. Rheum. Dis., 2017, Vol. 76, no. 2, pp. 16-17.Muller K., Herner E.B., Stagg A., Bendtzen K., Woo P. Inflammatory cytokines and cytokine antagonists in whole blood cultures of patients with systemic juvenile chronic arthritis. Br. J. Rheumatol., 1998, Vol. 37, no. 5, pp. 562-569.de Jager. Cytokines in juvenile idiopathic arthritis. Ann. Rheum. Dis., 2017, Vol. 76, no. 2, pp. 16-17.Opal S.M., DePalo V.A. Anti-inflammatory cytokines. Chest, 2000, Vol. 117, no. 4, pp. 1162-1172.de Jager, Hoppenreijs E.P.A.H., Wulffraat N.M., Wedderburn L.R, Kuis W., Prakken B.J. Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: a cross-sectional study. Ann. Rheum. Dis., 2007, no. 66, pp. 589-598.Paramalingam S.S., Thumboo J., Vasoo S., Thio S.T., Connie Tse C., Fong K-Y. In vivo pro- and antiinflammatory cytokines in normal and patients with rheumatoid arthritis. Ann. Acad. Med. Singapore, 2007, Vol. 36, pp. 96-99.de Jager, Hoppenreijs E.P.A.H., Wulffraat N.M., Wedderburn L.R, Kuis W., Prakken B.J. Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: a cross-sectional study. Ann. Rheum. Dis., 2007, no. 66, pp. 589-598.Park M.J., Lee S.H., Kim E.K., Lee E.J., Baek J.A., Park S.H., Kwok S.K., Cho M.L. Interleukin-10 produced by myeloid-derived suppressor cells is critical for the induction of Tregs and attenuation of rheumatoid inflammation in mice. Sci. Rep., 2018, Vol. 8, no. 1, p. 3753.Dong C., Fu T., Ji J., Li Z., Gu Z. The role of interleukin-4 in rheumatic diseases. Clin. Exp. Pharmacol. Physiol., 2018, Vol. 45, no. 8, pp. 747-754.Petra A.I., Tsilioni I., Taracanova A., Katsarou-Katsari A., Theoharides T.C. Interleukin 33 and interleukin 4 regulate interleukin 31 gene expression and secretion from human laboratory of allergic diseases 2 mast cells stimulated by substance P and/or immunoglobulin E. Allergy Asthma Proc., 2018, no. 39, pp. 153-160.Dong C., Fu T., Ji J., Li Z., Gu Z. The role of interleukin-4 in rheumatic diseases. Clin. Exp. Pharmacol. Physiol., 2018, Vol. 45, no. 8, pp. 747-754.Pignatti P., Vivarelli M., Meazza C., Rizzolo M.G., Martini A., De Benedetti F. Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis. J. Rheumatol., 2001, Vol. 28, no. 7, pp. 1670-1676.Guo L., Lu M.P., Dong G.J., Teng L.P., Xu Y.P., Zou L.X., Zheng Q. Clinical and laboratory features of macrophage activation syndrome. Zhongguo Dang Dai Er Ke Za Zhi, 2017, Vol. 19, no. 2, pp. 188-192.Prieur A.M., Roux-Lombard P., Dayer J.M. Dynamics of fever and the cytokine network in systemic juvenile arthritis. Rev. Rhum. Engl. Ed., 1996, Vol. 63, no. 3, рр. 163-170.Guo L., Lu M.P., Dong G.J., Teng L.P., Xu Y.P., Zou L.X., Zheng Q. Clinical and laboratory features of macrophage activation syndrome. Zhongguo Dang Dai Er Ke Za Zhi, 2017, Vol. 19, no. 2, pp. 188-192.Raziuddin S., Bahabri S., Al-Dalaan, Siraj A.K., Al-Sedairy S. A mixed Th1/Th2 cell cytokine response predominantes in systemic onset juvenile rheumatoid arthritis: immunoregulatory IL-10 function. Clin. Immunol. Immunopatol., 1998, no. 86, pp. 192-198.Guo L., Lu M.P., Tang Y.M., Teng L.P., Xu Y.P., Zou L.X., Zheng R.J., Zheng Q. Serum cytokine levels in children with newly diagnosed active systemic juvenile idiopathic arthritis. Zhongguo Dang Dai Er Ke Za Zhi, 2014, Vol. 16, no. 12, pp. 1241-1244.Sadeghi A., Pezeshgi A., Karimimoghaddam A., Moghimi M., Kamali K., Naseri M., Esmaeilzadeh A. Evaluation of anti-mutated citrullinated vimentin antibodies, anti-cyclic citrullinated peptide antibodies in patients with rheumatoid arthritis in comparison with other rheumatic diseases; a nephrology point of view. J. Nephropharmacol., 2017, Vol. 6, no. 2, рр. 98-105.Guo L., Lu M.P., Tang Y.M., Teng L.P., Xu Y.P., Zou L.X., Zheng R.J., Zheng Q. Serum cytokine levels in children with newly diagnosed active systemic juvenile idiopathic arthritis. Zhongguo Dang Dai Er Ke Za Zhi, 2014, Vol. 16, no. 12, pp. 1241-1244.Sapan H.B., Paturusi I., Jusuf I., Patellongi I., Massi M.N., Pusponegoro A.D., Arief S.K., Labeda I., Islam A.A., Rendy L., Hatta M. Pattern of cytokine (IL-6 and IL-10) level as inflammation and anti-inflammation mediator of multiple organ dysfunction syndrome (MODS) in polytrauma. Int. J. Burn Trauma, 2016, Vol. 6, no. 2, pp. 37-43.Gohar F., Kessel Ch., Lavric M., Holzinger D., Foell D. Review of biomarkers in systemic juvenile idiopathic arthritis: helpful tools or just playing tricks? Arthritis Res. Ther., 2016, Vol. 18, p. 163.Singh A.K., Misra R., Aggarwal A. Th-17 associated cytokines in patients with reactive arthritis/undifferentiated spondyloarthropathy. Clin. Rheumatol., 2011, Vol. 30, no. 6, pp. 771-776.Gohar F., Kessel Ch., Lavric M., Holzinger D., Foell D. Review of biomarkers in systemic juvenile idiopathic arthritis: helpful tools or just playing tricks? Arthritis Res. Ther., 2016, Vol. 18, p. 163.Shahin A.A., Shaker O.G., Kamal N., Hafez H.A., Gaber W., Shahin H.A. Circulating interleukin-6, soluble interleukin-2 receptors, tumor necrosis factor alpha, and interleukin-10 levels in juvenile chronic arthritis: correlations with soft tissue vascularity assessed by power Doppler sonography. Rheumatol Int., 2002, Vol. 22, no. 2, pp. 84-88.Harsini S., Ziaee V., Maddah M., Rezaei A., Sadr M., Zoghi S., Moradinejad M.H., Tahghighi F., Aghighi Y., Rezaei N. Interleukin 10 and transforming growth factor beta 1 gene polymorphisms in juvenile idiopathic arthritis. Bratisl. Med. J., 2016, Vol. 117, no. 5, рр. 258-262.Swart J.F, van Dijkhuizen E.H.P., Wulffraat N.M., Sytze de Roock. Clinical juvenile arthritis disease activity score proves to be a useful tool in treat-to-target therapy in juvenile idiopathic arthritis. Ann. Rheum. Dis., 2018, Vol. 77, pp. 336-342.Harsini S., Ziaee V., Maddah M., Rezaei A., Sadr M., Zoghi S., Moradinejad M.H., Tahghighi F., Aghighi Y., Rezaei N. Interleukin 10 and transforming growth factor beta 1 gene polymorphisms in juvenile idiopathic arthritis. Bratisl. Med. J., 2016, Vol. 117, no. 5, рр. 258-262.Tong Y., Yang T., Wang J., Zhao T., Wang L., Kang Y., Cheng C., Fan Y. Elevated plasma chemokines for eosinophils in neuromyelitis optica spectrum disorders during remission. Front. Neurol., 2018, Vol. 9, no. 44, pp. 1-7.Heney D., Whicher T.J. Factors affecting the measurement of cytokines in biological fluids: implications for their clinical measurement. Ann. Clin. Biochem., 1995, no. 32, pp. 358-368.Vastert S.J., de Jager W., Noordman B.J., Holzinger D., Kuis W., Prakken B.J., Wulffraat N.M. Effectiveness of first-line treatment with recombinant interleukin-1 receptor antagonist in steroid-naive patients with new-onset systemic juvenile idiopathic arthritis. Arthritis Rheumatol., 2014, Vol. 66, no. 4, pp. 1034-1043.Heney D., Whicher T.J. Factors affecting the measurement of cytokines in biological fluids: implications for their clinical measurement. Ann. Clin. Biochem., 1995, no. 32, pp. 358-368.Yamamoto A., Sato К., Miyoshi F., Shindo Y., Yoshida Y., Yokota K., Nakajima K., Akiba H., Asanuma Y., Akiyama Y., Mimura T. Analisis of cytokine production patterns of peripheriel blood mononuclear cells from a rheumatoid arthritis patient successfully treated witch rituximab. Mod. Rheumatol., 2010, no. 2, pp. 183-187.Hong K.H., Cho M.L., Min S.Y., Shin Y.J., Yoo S.A., Choi J.J., Kim W.U., Song S.W., Chо C.S. Effect of interleukin-4 on vascular endothelial growth factor production in rheumatoid synovial fibroblasts. Clin. Exp. Immunol., 2007, Vol. 147, no. 3, pp. 573-579.Yoshimura A., Wakabayashi Y., Mori T. Cellular and molecular basis for the regulation of inflammation by TGF-beta. J. Biochem., 2010, Vol. 147, no. 6, рр. 781-792.Hong K.H., Cho M.L., Min S.Y., Shin Y.J., Yoo S.A., Choi J.J., Kim W.U., Song S.W., Chо C.S. Effect of interleukin-4 on vascular endothelial growth factor production in rheumatoid synovial fibroblasts. Clin. Exp. Immunol., 2007, Vol. 147, no. 3, pp. 573-579.Yu F.Y., Xie C.Q., Jiang C.L., Sun J.T., Huang X.W. TNFα increases inflammatory factor expression in synovial fibroblasts through the toll like receptor 3 mediated ERK/AKT signaling pathway in a mouse model of rheumatoid arthritis. Mol. Med. Rep., 2018, Vol. 17, no. 6, pp. 8475-8483.Horai R., Saijo S., Tanioka H., Nakae S., Sudo K., Okahara A., Ikuse T., Asano M., Iwakura Y. Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice. J. Exp. Med., 2000, Vol. 191, no. 2, рр. 313-320.Horai R., Saijo S., Tanioka H., Nakae S., Sudo K., Okahara A., Ikuse T., Asano M., Iwakura Y. Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice. J. Exp. Med., 2000, Vol. 191, no. 2, рр. 313-320.Horai R., Saijo S., Tanioka H., Nakae S., Sudo K., Okahara A., Ikuse T., Asano M., Iwakura Y. Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice. J. Exp. Med., 2000, Vol. 191, no. 2, рр. 313-320.Huang J.L., Kuo M.L., Hung I.J., Wu C.J., Ou L.H., Cheng J.H. Lowered IL-4-producing T cells and decreased IL-4 secretion in peripheral blood from subjects with juvenile rheumatoid arthritis. Chang Gung Med. J., 2001, Vol. 24, no. 2, pp. 77-83.Huang J.L., Kuo M.L., Hung I.J., Wu C.J., Ou L.H., Cheng J.H. Lowered IL-4-producing T cells and decreased IL-4 secretion in peripheral blood from subjects with juvenile rheumatoid arthritis. Chang Gung Med. J., 2001, Vol. 24, no. 2, pp. 77-83.Huang J.L., Kuo M.L., Hung I.J., Wu C.J., Ou L.H., Cheng J.H. Lowered IL-4-producing T cells and decreased IL-4 secretion in peripheral blood from subjects with juvenile rheumatoid arthritis. Chang Gung Med. J., 2001, Vol. 24, no. 2, pp. 77-83.Huang J.L., Kuo M.L., Hung I.J., Wu C.J., Ou L.H., Cheng J.H. Lowered IL-4-producing T cells and decreased IL-4 secretion in peripheral blood from subjects with juvenile rheumatoid arthritis. Chang Gung Med. J., 2001, Vol. 24, no. 2, pp. 77-83.Johdi N.A., Mazlan L., Sagap I., Jamal R. Profiling of cytokines, chemokines and other soluble proteins as a potential biomarker in colorectal cancer and polyps. Cytokine, 2017, no. 99, рр. 35-42.Johdi N.A., Mazlan L., Sagap I., Jamal R. Profiling of cytokines, chemokines and other soluble proteins as a potential biomarker in colorectal cancer and polyps. Cytokine, 2017, no. 99, рр. 35-42.Johdi N.A., Mazlan L., Sagap I., Jamal R. Profiling of cytokines, chemokines and other soluble proteins as a potential biomarker in colorectal cancer and polyps. Cytokine, 2017, no. 99, рр. 35-42.Johdi N.A., Mazlan L., Sagap I., Jamal R. Profiling of cytokines, chemokines and other soluble proteins as a potential biomarker in colorectal cancer and polyps. Cytokine, 2017, no. 99, рр. 35-42.Kawasumi H., Gono T., Tanaka E., Kaneko H., Kawaguchi Y., Yamanaka H. Clinical characteristics and cytokine profiles of organizing pneumonia in patients with rheumatoid arthritis treated with or without biologics. J. Rheumatol., 2014, Vol. 43, no. 4, pp. 738-744.Kawasumi H., Gono T., Tanaka E., Kaneko H., Kawaguchi Y., Yamanaka H. Clinical characteristics and cytokine profiles of organizing pneumonia in patients with rheumatoid arthritis treated with or without biologics. J. Rheumatol., 2014, Vol. 43, no. 4, pp. 738-744.Kawasumi H., Gono T., Tanaka E., Kaneko H., Kawaguchi Y., Yamanaka H. Clinical characteristics and cytokine profiles of organizing pneumonia in patients with rheumatoid arthritis treated with or without biologics. J. Rheumatol., 2014, Vol. 43, no. 4, pp. 738-744.Kawasumi H., Gono T., Tanaka E., Kaneko H., Kawaguchi Y., Yamanaka H. Clinical characteristics and cytokine profiles of organizing pneumonia in patients with rheumatoid arthritis treated with or without biologics. J. Rheumatol., 2014, Vol. 43, no. 4, pp. 738-744.Kutukculer N., Caglayan S., Aydogdu F. Study of pro-inflammatory (TNF-alpha, IL-1alpha, IL-6) and T-cellderived (IL-2, IL-4) cytokines in plasma and synovial fluid of patients with juvenile chronic arthritis: correlations with clinical and laboratory parameters. Clin. Rheumatol., 1998, Vol. 17, no. 4, pp. 288-292.Kutukculer N., Caglayan S., Aydogdu F. Study of pro-inflammatory (TNF-alpha, IL-1alpha, IL-6) and T-cellderived (IL-2, IL-4) cytokines in plasma and synovial fluid of patients with juvenile chronic arthritis: correlations with clinical and laboratory parameters. Clin. Rheumatol., 1998, Vol. 17, no. 4, pp. 288-292.Kutukculer N., Caglayan S., Aydogdu F. Study of pro-inflammatory (TNF-alpha, IL-1alpha, IL-6) and T-cellderived (IL-2, IL-4) cytokines in plasma and synovial fluid of patients with juvenile chronic arthritis: correlations with clinical and laboratory parameters. Clin. Rheumatol., 1998, Vol. 17, no. 4, pp. 288-292.Kutukculer N., Caglayan S., Aydogdu F. Study of pro-inflammatory (TNF-alpha, IL-1alpha, IL-6) and T-cellderived (IL-2, IL-4) cytokines in plasma and synovial fluid of patients with juvenile chronic arthritis: correlations with clinical and laboratory parameters. Clin. Rheumatol., 1998, Vol. 17, no. 4, pp. 288-292.Lee C.K., Lee E.Y., Chung S.M., Mun S.H., Yoo B., Moon H.B. Effects of disease-modifying antirheumatic drugs and antiinflammatory cytokines on human osteoclastogenesis through interaction with receptor activator of nuclear factor kappa B, osteoprotegerin, and receptor activator of nuclear factor kappa B ligand. Arthritis Rheum., 2004, Vol. 50, no. 12, pp. 3831-3843.Lee C.K., Lee E.Y., Chung S.M., Mun S.H., Yoo B., Moon H.B. Effects of disease-modifying antirheumatic drugs and antiinflammatory cytokines on human osteoclastogenesis through interaction with receptor activator of nuclear factor kappa B, osteoprotegerin, and receptor activator of nuclear factor kappa B ligand. Arthritis Rheum., 2004, Vol. 50, no. 12, pp. 3831-3843.Lee C.K., Lee E.Y., Chung S.M., Mun S.H., Yoo B., Moon H.B. Effects of disease-modifying antirheumatic drugs and antiinflammatory cytokines on human osteoclastogenesis through interaction with receptor activator of nuclear factor kappa B, osteoprotegerin, and receptor activator of nuclear factor kappa B ligand. Arthritis Rheum., 2004, Vol. 50, no. 12, pp. 3831-3843.Lee C.K., Lee E.Y., Chung S.M., Mun S.H., Yoo B., Moon H.B. Effects of disease-modifying antirheumatic drugs and antiinflammatory cytokines on human osteoclastogenesis through interaction with receptor activator of nuclear factor kappa B, osteoprotegerin, and receptor activator of nuclear factor kappa B ligand. Arthritis Rheum., 2004, Vol. 50, no. 12, pp. 3831-3843.Lijiao J., Meiping L.U., Li G., Jianqiang W.U., Lixia Z., Yiping X.U. Serum levels of Th1/Th2 cytokines in children with non-systemic juvenile idiopathic arthritis. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2016, Vol. 45, no. 3, pp. 281-286.Lijiao J., Meiping L.U., Li G., Jianqiang W.U., Lixia Z., Yiping X.U. Serum levels of Th1/Th2 cytokines in children with non-systemic juvenile idiopathic arthritis. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2016, Vol. 45, no. 3, pp. 281-286.Lijiao J., Meiping L.U., Li G., Jianqiang W.U., Lixia Z., Yiping X.U. Serum levels of Th1/Th2 cytokines in children with non-systemic juvenile idiopathic arthritis. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2016, Vol. 45, no. 3, pp. 281-286.Lijiao J., Meiping L.U., Li G., Jianqiang W.U., Lixia Z., Yiping X.U. Serum levels of Th1/Th2 cytokines in children with non-systemic juvenile idiopathic arthritis. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2016, Vol. 45, no. 3, pp. 281-286.Muller K., Herner E.B., Stagg A., Bendtzen K., Woo P. Inflammatory cytokines and cytokine antagonists in whole blood cultures of patients with systemic juvenile chronic arthritis. Br. J. Rheumatol., 1998, Vol. 37, no. 5, pp. 562-569.Muller K., Herner E.B., Stagg A., Bendtzen K., Woo P. Inflammatory cytokines and cytokine antagonists in whole blood cultures of patients with systemic juvenile chronic arthritis. Br. J. Rheumatol., 1998, Vol. 37, no. 5, pp. 562-569.Muller K., Herner E.B., Stagg A., Bendtzen K., Woo P. Inflammatory cytokines and cytokine antagonists in whole blood cultures of patients with systemic juvenile chronic arthritis. Br. J. Rheumatol., 1998, Vol. 37, no. 5, pp. 562-569.Muller K., Herner E.B., Stagg A., Bendtzen K., Woo P. Inflammatory cytokines and cytokine antagonists in whole blood cultures of patients with systemic juvenile chronic arthritis. Br. J. Rheumatol., 1998, Vol. 37, no. 5, pp. 562-569.Opal S.M., DePalo V.A. Anti-inflammatory cytokines. Chest, 2000, Vol. 117, no. 4, pp. 1162-1172.Opal S.M., DePalo V.A. Anti-inflammatory cytokines. Chest, 2000, Vol. 117, no. 4, pp. 1162-1172.Opal S.M., DePalo V.A. Anti-inflammatory cytokines. Chest, 2000, Vol. 117, no. 4, pp. 1162-1172.Opal S.M., DePalo V.A. Anti-inflammatory cytokines. Chest, 2000, Vol. 117, no. 4, pp. 1162-1172.Paramalingam S.S., Thumboo J., Vasoo S., Thio S.T., Connie Tse C., Fong K-Y. In vivo pro- and antiinflammatory cytokines in normal and patients with rheumatoid arthritis. Ann. Acad. Med. Singapore, 2007, Vol. 36, pp. 96-99.Paramalingam S.S., Thumboo J., Vasoo S., Thio S.T., Connie Tse C., Fong K-Y. In vivo pro- and antiinflammatory cytokines in normal and patients with rheumatoid arthritis. Ann. Acad. Med. Singapore, 2007, Vol. 36, pp. 96-99.Paramalingam S.S., Thumboo J., Vasoo S., Thio S.T., Connie Tse C., Fong K-Y. In vivo pro- and antiinflammatory cytokines in normal and patients with rheumatoid arthritis. Ann. Acad. Med. Singapore, 2007, Vol. 36, pp. 96-99.Paramalingam S.S., Thumboo J., Vasoo S., Thio S.T., Connie Tse C., Fong K-Y. In vivo pro- and antiinflammatory cytokines in normal and patients with rheumatoid arthritis. Ann. Acad. Med. Singapore, 2007, Vol. 36, pp. 96-99.Park M.J., Lee S.H., Kim E.K., Lee E.J., Baek J.A., Park S.H., Kwok S.K., Cho M.L. Interleukin-10 produced by myeloid-derived suppressor cells is critical for the induction of Tregs and attenuation of rheumatoid inflammation in mice. Sci. Rep., 2018, Vol. 8, no. 1, p. 3753.Park M.J., Lee S.H., Kim E.K., Lee E.J., Baek J.A., Park S.H., Kwok S.K., Cho M.L. Interleukin-10 produced by myeloid-derived suppressor cells is critical for the induction of Tregs and attenuation of rheumatoid inflammation in mice. Sci. Rep., 2018, Vol. 8, no. 1, p. 3753.Park M.J., Lee S.H., Kim E.K., Lee E.J., Baek J.A., Park S.H., Kwok S.K., Cho M.L. Interleukin-10 produced by myeloid-derived suppressor cells is critical for the induction of Tregs and attenuation of rheumatoid inflammation in mice. Sci. Rep., 2018, Vol. 8, no. 1, p. 3753.Park M.J., Lee S.H., Kim E.K., Lee E.J., Baek J.A., Park S.H., Kwok S.K., Cho M.L. Interleukin-10 produced by myeloid-derived suppressor cells is critical for the induction of Tregs and attenuation of rheumatoid inflammation in mice. Sci. Rep., 2018, Vol. 8, no. 1, p. 3753.Petra A.I., Tsilioni I., Taracanova A., Katsarou-Katsari A., Theoharides T.C. Interleukin 33 and interleukin 4 regulate interleukin 31 gene expression and secretion from human laboratory of allergic diseases 2 mast cells stimulated by substance P and/or immunoglobulin E. Allergy Asthma Proc., 2018, no. 39, pp. 153-160.Petra A.I., Tsilioni I., Taracanova A., Katsarou-Katsari A., Theoharides T.C. Interleukin 33 and interleukin 4 regulate interleukin 31 gene expression and secretion from human laboratory of allergic diseases 2 mast cells stimulated by substance P and/or immunoglobulin E. Allergy Asthma Proc., 2018, no. 39, pp. 153-160.Petra A.I., Tsilioni I., Taracanova A., Katsarou-Katsari A., Theoharides T.C. Interleukin 33 and interleukin 4 regulate interleukin 31 gene expression and secretion from human laboratory of allergic diseases 2 mast cells stimulated by substance P and/or immunoglobulin E. Allergy Asthma Proc., 2018, no. 39, pp. 153-160.Petra A.I., Tsilioni I., Taracanova A., Katsarou-Katsari A., Theoharides T.C. Interleukin 33 and interleukin 4 regulate interleukin 31 gene expression and secretion from human laboratory of allergic diseases 2 mast cells stimulated by substance P and/or immunoglobulin E. Allergy Asthma Proc., 2018, no. 39, pp. 153-160.Pignatti P., Vivarelli M., Meazza C., Rizzolo M.G., Martini A., De Benedetti F. Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis. J. Rheumatol., 2001, Vol. 28, no. 7, pp. 1670-1676.Pignatti P., Vivarelli M., Meazza C., Rizzolo M.G., Martini A., De Benedetti F. Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis. J. Rheumatol., 2001, Vol. 28, no. 7, pp. 1670-1676.Pignatti P., Vivarelli M., Meazza C., Rizzolo M.G., Martini A., De Benedetti F. Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis. J. Rheumatol., 2001, Vol. 28, no. 7, pp. 1670-1676.Pignatti P., Vivarelli M., Meazza C., Rizzolo M.G., Martini A., De Benedetti F. Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis. J. Rheumatol., 2001, Vol. 28, no. 7, pp. 1670-1676.Prieur A.M., Roux-Lombard P., Dayer J.M. Dynamics of fever and the cytokine network in systemic juvenile arthritis. Rev. Rhum. Engl. Ed., 1996, Vol. 63, no. 3, рр. 163-170.Prieur A.M., Roux-Lombard P., Dayer J.M. Dynamics of fever and the cytokine network in systemic juvenile arthritis. Rev. Rhum. Engl. Ed., 1996, Vol. 63, no. 3, рр. 163-170.Prieur A.M., Roux-Lombard P., Dayer J.M. Dynamics of fever and the cytokine network in systemic juvenile arthritis. Rev. Rhum. Engl. Ed., 1996, Vol. 63, no. 3, рр. 163-170.Prieur A.M., Roux-Lombard P., Dayer J.M. Dynamics of fever and the cytokine network in systemic juvenile arthritis. Rev. Rhum. Engl. Ed., 1996, Vol. 63, no. 3, рр. 163-170.Raziuddin S., Bahabri S., Al-Dalaan, Siraj A.K., Al-Sedairy S. A mixed Th1/Th2 cell cytokine response predominantes in systemic onset juvenile rheumatoid arthritis: immunoregulatory IL-10 function. Clin. Immunol. Immunopatol., 1998, no. 86, pp. 192-198.Raziuddin S., Bahabri S., Al-Dalaan, Siraj A.K., Al-Sedairy S. A mixed Th1/Th2 cell cytokine response predominantes in systemic onset juvenile rheumatoid arthritis: immunoregulatory IL-10 function. Clin. Immunol. Immunopatol., 1998, no. 86, pp. 192-198.Raziuddin S., Bahabri S., Al-Dalaan, Siraj A.K., Al-Sedairy S. A mixed Th1/Th2 cell cytokine response predominantes in systemic onset juvenile rheumatoid arthritis: immunoregulatory IL-10 function. Clin. Immunol. Immunopatol., 1998, no. 86, pp. 192-198.Raziuddin S., Bahabri S., Al-Dalaan, Siraj A.K., Al-Sedairy S. A mixed Th1/Th2 cell cytokine response predominantes in systemic onset juvenile rheumatoid arthritis: immunoregulatory IL-10 function. Clin. Immunol. Immunopatol., 1998, no. 86, pp. 192-198.Sadeghi A., Pezeshgi A., Karimimoghaddam A., Moghimi M., Kamali K., Naseri M., Esmaeilzadeh A. Evaluation of anti-mutated citrullinated vimentin antibodies, anti-cyclic citrullinated peptide antibodies in patients with rheumatoid arthritis in comparison with other rheumatic diseases; a nephrology point of view. J. Nephropharmacol., 2017, Vol. 6, no. 2, рр. 98-105.Sadeghi A., Pezeshgi A., Karimimoghaddam A., Moghimi M., Kamali K., Naseri M., Esmaeilzadeh A. Evaluation of anti-mutated citrullinated vimentin antibodies, anti-cyclic citrullinated peptide antibodies in patients with rheumatoid arthritis in comparison with other rheumatic diseases; a nephrology point of view. J. Nephropharmacol., 2017, Vol. 6, no. 2, рр. 98-105.Sadeghi A., Pezeshgi A., Karimimoghaddam A., Moghimi M., Kamali K., Naseri M., Esmaeilzadeh A. Evaluation of anti-mutated citrullinated vimentin antibodies, anti-cyclic citrullinated peptide antibodies in patients with rheumatoid arthritis in comparison with other rheumatic diseases; a nephrology point of view. J. Nephropharmacol., 2017, Vol. 6, no. 2, рр. 98-105.Sadeghi A., Pezeshgi A., Karimimoghaddam A., Moghimi M., Kamali K., Naseri M., Esmaeilzadeh A. Evaluation of anti-mutated citrullinated vimentin antibodies, anti-cyclic citrullinated peptide antibodies in patients with rheumatoid arthritis in comparison with other rheumatic diseases; a nephrology point of view. J. Nephropharmacol., 2017, Vol. 6, no. 2, рр. 98-105.Sapan H.B., Paturusi I., Jusuf I., Patellongi I., Massi M.N., Pusponegoro A.D., Arief S.K., Labeda I., Islam A.A., Rendy L., Hatta M. Pattern of cytokine (IL-6 and IL-10) level as inflammation and anti-inflammation mediator of multiple organ dysfunction syndrome (MODS) in polytrauma. Int. J. Burn Trauma, 2016, Vol. 6, no. 2, pp. 37-43.Sapan H.B., Paturusi I., Jusuf I., Patellongi I., Massi M.N., Pusponegoro A.D., Arief S.K., Labeda I., Islam A.A., Rendy L., Hatta M. Pattern of cytokine (IL-6 and IL-10) level as inflammation and anti-inflammation mediator of multiple organ dysfunction syndrome (MODS) in polytrauma. Int. J. Burn Trauma, 2016, Vol. 6, no. 2, pp. 37-43.Sapan H.B., Paturusi I., Jusuf I., Patellongi I., Massi M.N., Pusponegoro A.D., Arief S.K., Labeda I., Islam A.A., Rendy L., Hatta M. Pattern of cytokine (IL-6 and IL-10) level as inflammation and anti-inflammation mediator of multiple organ dysfunction syndrome (MODS) in polytrauma. Int. J. Burn Trauma, 2016, Vol. 6, no. 2, pp. 37-43.Sapan H.B., Paturusi I., Jusuf I., Patellongi I., Massi M.N., Pusponegoro A.D., Arief S.K., Labeda I., Islam A.A., Rendy L., Hatta M. Pattern of cytokine (IL-6 and IL-10) level as inflammation and anti-inflammation mediator of multiple organ dysfunction syndrome (MODS) in polytrauma. Int. J. Burn Trauma, 2016, Vol. 6, no. 2, pp. 37-43.Singh A.K., Misra R., Aggarwal A. Th-17 associated cytokines in patients with reactive arthritis/undifferentiated spondyloarthropathy. Clin. Rheumatol., 2011, Vol. 30, no. 6, pp. 771-776.Singh A.K., Misra R., Aggarwal A. Th-17 associated cytokines in patients with reactive arthritis/undifferentiated spondyloarthropathy. Clin. Rheumatol., 2011, Vol. 30, no. 6, pp. 771-776.Singh A.K., Misra R., Aggarwal A. Th-17 associated cytokines in patients with reactive arthritis/undifferentiated spondyloarthropathy. Clin. Rheumatol., 2011, Vol. 30, no. 6, pp. 771-776.Singh A.K., Misra R., Aggarwal A. Th-17 associated cytokines in patients with reactive arthritis/undifferentiated spondyloarthropathy. Clin. Rheumatol., 2011, Vol. 30, no. 6, pp. 771-776.Singh A.K., Misra R., Aggarwal A. Th-17 associated cytokines in patients with reactive arthritis/undifferentiated spondyloarthropathy. Clin. Rheumatol., 2011, Vol. 30, no. 6, pp. 771-776.Singh A.K., Misra R., Aggarwal A. Th-17 associated cytokines in patients with reactive arthritis/undifferentiated spondyloarthropathy. Clin. Rheumatol., 2011, Vol. 30, no. 6, pp. 771-776.Shahin A.A., Shaker O.G., Kamal N., Hafez H.A., Gaber W., Shahin H.A. Circulating interleukin-6, soluble interleukin-2 receptors, tumor necrosis factor alpha, and interleukin-10 levels in juvenile chronic arthritis: correlations with soft tissue vascularity assessed by power Doppler sonography. Rheumatol Int., 2002, Vol. 22, no. 2, pp. 84-88.Shahin A.A., Shaker O.G., Kamal N., Hafez H.A., Gaber W., Shahin H.A. Circulating interleukin-6, soluble interleukin-2 receptors, tumor necrosis factor alpha, and interleukin-10 levels in juvenile chronic arthritis: correlations with soft tissue vascularity assessed by power Doppler sonography. Rheumatol Int., 2002, Vol. 22, no. 2, pp. 84-88.Shahin A.A., Shaker O.G., Kamal N., Hafez H.A., Gaber W., Shahin H.A. Circulating interleukin-6, soluble interleukin-2 receptors, tumor necrosis factor alpha, and interleukin-10 levels in juvenile chronic arthritis: correlations with soft tissue vascularity assessed by power Doppler sonography. Rheumatol Int., 2002, Vol. 22, no. 2, pp. 84-88.Shahin A.A., Shaker O.G., Kamal N., Hafez H.A., Gaber W., Shahin H.A. Circulating interleukin-6, soluble interleukin-2 receptors, tumor necrosis factor alpha, and interleukin-10 levels in juvenile chronic arthritis: correlations with soft tissue vascularity assessed by power Doppler sonography. Rheumatol Int., 2002, Vol. 22, no. 2, pp. 84-88.Shahin A.A., Shaker O.G., Kamal N., Hafez H.A., Gaber W., Shahin H.A. Circulating interleukin-6, soluble interleukin-2 receptors, tumor necrosis factor alpha, and interleukin-10 levels in juvenile chronic arthritis: correlations with soft tissue vascularity assessed by power Doppler sonography. Rheumatol Int., 2002, Vol. 22, no. 2, pp. 84-88.Shahin A.A., Shaker O.G., Kamal N., Hafez H.A., Gaber W., Shahin H.A. Circulating interleukin-6, soluble interleukin-2 receptors, tumor necrosis factor alpha, and interleukin-10 levels in juvenile chronic arthritis: correlations with soft tissue vascularity assessed by power Doppler sonography. Rheumatol Int., 2002, Vol. 22, no. 2, pp. 84-88.Swart J.F, van Dijkhuizen E.H.P., Wulffraat N.M., Sytze de Roock. Clinical juvenile arthritis disease activity score proves to be a useful tool in treat-to-target therapy in juvenile idiopathic arthritis. Ann. Rheum. Dis., 2018, Vol. 77, pp. 336-342.Swart J.F, van Dijkhuizen E.H.P., Wulffraat N.M., Sytze de Roock. Clinical juvenile arthritis disease activity score proves to be a useful tool in treat-to-target therapy in juvenile idiopathic arthritis. Ann. Rheum. Dis., 2018, Vol. 77, pp. 336-342.Swart J.F, van Dijkhuizen E.H.P., Wulffraat N.M., Sytze de Roock. Clinical juvenile arthritis disease activity score proves to be a useful tool in treat-to-target therapy in juvenile idiopathic arthritis. Ann. Rheum. Dis., 2018, Vol. 77, pp. 336-342.Swart J.F, van Dijkhuizen E.H.P., Wulffraat N.M., Sytze de Roock. Clinical juvenile arthritis disease activity score proves to be a useful tool in treat-to-target therapy in juvenile idiopathic arthritis. Ann. Rheum. Dis., 2018, Vol. 77, pp. 336-342.Swart J.F, van Dijkhuizen E.H.P., Wulffraat N.M., Sytze de Roock. Clinical juvenile arthritis disease activity score proves to be a useful tool in treat-to-target therapy in juvenile idiopathic arthritis. Ann. Rheum. Dis., 2018, Vol. 77, pp. 336-342.Swart J.F, van Dijkhuizen E.H.P., Wulffraat N.M., Sytze de Roock. Clinical juvenile arthritis disease activity score proves to be a useful tool in treat-to-target therapy in juvenile idiopathic arthritis. Ann. Rheum. Dis., 2018, Vol. 77, pp. 336-342.Tong Y., Yang T., Wang J., Zhao T., Wang L., Kang Y., Cheng C., Fan Y. Elevated plasma chemokines for eosinophils in neuromyelitis optica spectrum disorders during remission. Front. Neurol., 2018, Vol. 9, no. 44, pp. 1-7.Tong Y., Yang T., Wang J., Zhao T., Wang L., Kang Y., Cheng C., Fan Y. Elevated plasma chemokines for eosinophils in neuromyelitis optica spectrum disorders during remission. Front. Neurol., 2018, Vol. 9, no. 44, pp. 1-7.Tong Y., Yang T., Wang J., Zhao T., Wang L., Kang Y., Cheng C., Fan Y. Elevated plasma chemokines for eosinophils in neuromyelitis optica spectrum disorders during remission. Front. Neurol., 2018, Vol. 9, no. 44, pp. 1-7.Tong Y., Yang T., Wang J., Zhao T., Wang L., Kang Y., Cheng C., Fan Y. Elevated plasma chemokines for eosinophils in neuromyelitis optica spectrum disorders during remission. Front. Neurol., 2018, Vol. 9, no. 44, pp. 1-7.Tong Y., Yang T., Wang J., Zhao T., Wang L., Kang Y., Cheng C., Fan Y. Elevated plasma chemokines for eosinophils in neuromyelitis optica spectrum disorders during remission. Front. Neurol., 2018, Vol. 9, no. 44, pp. 1-7.Tong Y., Yang T., Wang J., Zhao T., Wang L., Kang Y., Cheng C., Fan Y. Elevated plasma chemokines for eosinophils in neuromyelitis optica spectrum disorders during remission. Front. Neurol., 2018, Vol. 9, no. 44, pp. 1-7.Vastert S.J., de Jager W., Noordman B.J., Holzinger D., Kuis W., Prakken B.J., Wulffraat N.M. Effectiveness of first-line treatment with recombinant interleukin-1 receptor antagonist in steroid-naive patients with new-onset systemic juvenile idiopathic arthritis. Arthritis Rheumatol., 2014, Vol. 66, no. 4, pp. 1034-1043.Vastert S.J., de Jager W., Noordman B.J., Holzinger D., Kuis W., Prakken B.J., Wulffraat N.M. Effectiveness of first-line treatment with recombinant interleukin-1 receptor antagonist in steroid-naive patients with new-onset systemic juvenile idiopathic arthritis. Arthritis Rheumatol., 2014, Vol. 66, no. 4, pp. 1034-1043.Vastert S.J., de Jager W., Noordman B.J., Holzinger D., Kuis W., Prakken B.J., Wulffraat N.M. Effectiveness of first-line treatment with recombinant interleukin-1 receptor antagonist in steroid-naive patients with new-onset systemic juvenile idiopathic arthritis. Arthritis Rheumatol., 2014, Vol. 66, no. 4, pp. 1034-1043.Vastert S.J., de Jager W., Noordman B.J., Holzinger D., Kuis W., Prakken B.J., Wulffraat N.M. Effectiveness of first-line treatment with recombinant interleukin-1 receptor antagonist in steroid-naive patients with new-onset systemic juvenile idiopathic arthritis. Arthritis Rheumatol., 2014, Vol. 66, no. 4, pp. 1034-1043.Vastert S.J., de Jager W., Noordman B.J., Holzinger D., Kuis W., Prakken B.J., Wulffraat N.M. Effectiveness of first-line treatment with recombinant interleukin-1 receptor antagonist in steroid-naive patients with new-onset systemic juvenile idiopathic arthritis. Arthritis Rheumatol., 2014, Vol. 66, no. 4, pp. 1034-1043.Vastert S.J., de Jager W., Noordman B.J., Holzinger D., Kuis W., Prakken B.J., Wulffraat N.M. Effectiveness of first-line treatment with recombinant interleukin-1 receptor antagonist in steroid-naive patients with new-onset systemic juvenile idiopathic arthritis. Arthritis Rheumatol., 2014, Vol. 66, no. 4, pp. 1034-1043.Yamamoto A., Sato К., Miyoshi F., Shindo Y., Yoshida Y., Yokota K., Nakajima K., Akiba H., Asanuma Y., Akiyama Y., Mimura T. Analisis of cytokine production patterns of peripheriel blood mononuclear cells from a rheumatoid arthritis patient successfully treated witch rituximab. Mod. Rheumatol., 2010, no. 2, pp. 183-187.Yamamoto A., Sato К., Miyoshi F., Shindo Y., Yoshida Y., Yokota K., Nakajima K., Akiba H., Asanuma Y., Akiyama Y., Mimura T. Analisis of cytokine production patterns of peripheriel blood mononuclear cells from a rheumatoid arthritis patient successfully treated witch rituximab. Mod. Rheumatol., 2010, no. 2, pp. 183-187.Yamamoto A., Sato К., Miyoshi F., Shindo Y., Yoshida Y., Yokota K., Nakajima K., Akiba H., Asanuma Y., Akiyama Y., Mimura T. Analisis of cytokine production patterns of peripheriel blood mononuclear cells from a rheumatoid arthritis patient successfully treated witch rituximab. Mod. Rheumatol., 2010, no. 2, pp. 183-187.Yamamoto A., Sato К., Miyoshi F., Shindo Y., Yoshida Y., Yokota K., Nakajima K., Akiba H., Asanuma Y., Akiyama Y., Mimura T. Analisis of cytokine production patterns of peripheriel blood mononuclear cells from a rheumatoid arthritis patient successfully treated witch rituximab. Mod. Rheumatol., 2010, no. 2, pp. 183-187.Yamamoto A., Sato К., Miyoshi F., Shindo Y., Yoshida Y., Yokota K., Nakajima K., Akiba H., Asanuma Y., Akiyama Y., Mimura T. Analisis of cytokine production patterns of peripheriel blood mononuclear cells from a rheumatoid arthritis patient successfully treated witch rituximab. Mod. Rheumatol., 2010, no. 2, pp. 183-187.Yamamoto A., Sato К., Miyoshi F., Shindo Y., Yoshida Y., Yokota K., Nakajima K., Akiba H., Asanuma Y., Akiyama Y., Mimura T. Analisis of cytokine production patterns of peripheriel blood mononuclear cells from a rheumatoid arthritis patient successfully treated witch rituximab. Mod. Rheumatol., 2010, no. 2, pp. 183-187.Yoshimura A., Wakabayashi Y., Mori T. Cellular and molecular basis for the regulation of inflammation by TGF-beta. J. Biochem., 2010, Vol. 147, no. 6, рр. 781-792.Yoshimura A., Wakabayashi Y., Mori T. Cellular and molecular basis for the regulation of inflammation by TGF-beta. J. Biochem., 2010, Vol. 147, no. 6, рр. 781-792.Yoshimura A., Wakabayashi Y., Mori T. Cellular and molecular basis for the regulation of inflammation by TGF-beta. J. Biochem., 2010, Vol. 147, no. 6, рр. 781-792.Yoshimura A., Wakabayashi Y., Mori T. Cellular and molecular basis for the regulation of inflammation by TGF-beta. J. Biochem., 2010, Vol. 147, no. 6, рр. 781-792.Yoshimura A., Wakabayashi Y., Mori T. Cellular and molecular basis for the regulation of inflammation by TGF-beta. J. Biochem., 2010, Vol. 147, no. 6, рр. 781-792.Yoshimura A., Wakabayashi Y., Mori T. Cellular and molecular basis for the regulation of inflammation by TGF-beta. J. Biochem., 2010, Vol. 147, no. 6, рр. 781-792.Yu F.Y., Xie C.Q., Jiang C.L., Sun J.T., Huang X.W. TNFα increases inflammatory factor expression in synovial fibroblasts through the toll like receptor 3 mediated ERK/AKT signaling pathway in a mouse model of rheumatoid arthritis. Mol. Med. Rep., 2018, Vol. 17, no. 6, pp. 8475-8483.Yu F.Y., Xie C.Q., Jiang C.L., Sun J.T., Huang X.W. TNFα increases inflammatory factor expression in synovial fibroblasts through the toll like receptor 3 mediated ERK/AKT signaling pathway in a mouse model of rheumatoid arthritis. Mol. Med. Rep., 2018, Vol. 17, no. 6, pp. 8475-8483.Yu F.Y., Xie C.Q., Jiang C.L., Sun J.T., Huang X.W. TNFα increases inflammatory factor expression in synovial fibroblasts through the toll like receptor 3 mediated ERK/AKT signaling pathway in a mouse model of rheumatoid arthritis. Mol. Med. Rep., 2018, Vol. 17, no. 6, pp. 8475-8483.Yu F.Y., Xie C.Q., Jiang C.L., Sun J.T., Huang X.W. TNFα increases inflammatory factor expression in synovial fibroblasts through the toll like receptor 3 mediated ERK/AKT signaling pathway in a mouse model of rheumatoid arthritis. Mol. Med. Rep., 2018, Vol. 17, no. 6, pp. 8475-8483.Yu F.Y., Xie C.Q., Jiang C.L., Sun J.T., Huang X.W. TNFα increases inflammatory factor expression in synovial fibroblasts through the toll like receptor 3 mediated ERK/AKT signaling pathway in a mouse model of rheumatoid arthritis. Mol. Med. Rep., 2018, Vol. 17, no. 6, pp. 8475-8483.Yu F.Y., Xie C.Q., Jiang C.L., Sun J.T., Huang X.W. TNFα increases inflammatory factor expression in synovial fibroblasts through the toll like receptor 3 mediated ERK/AKT signaling pathway in a mouse model of rheumatoid arthritis. Mol. Med. Rep., 2018, Vol. 17, no. 6, pp. 8475-8483.

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