mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-LAS-1802mimmun-1802Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESЛокальная и системная продукция 45 цитокинов при осложненной пролиферативной диабетической ретинопатииLocal and systemic production of 45 cytokines in complicated proliferative diabetic retinopatyНероевВ. В.NeroevV. V.

Нероев Владимир Владимирович — докторр медицинских наук, профессор, член-корр. РАН, директор.

Москва

 

PhD, MD (Medicine), Professor, Corresponding Member.

Moscow

balnat07@rambler.ruЗайцеваО. В.ZaytsevaO. V.

Зайцева Ольга Владимировна — кандидат медицинских наук, заместитель директора.

Москва

PhD (Medicine), Deputy Director.

Moscow

balnat07@rambler.ruБалацкаяН. В.BalatskayaN. V.

Балацкая Наталья Владимировна— кандидат биологических наук, ведущий научный сотрудник отдела иммунологии и вирусологии.

105062, Москва, ул. Садовая-Черногрязская, 14/19, Тел.: 8 (916) 976-61-27

Balatskaya Natalia V. - PhD (Biology), Leading Research Associate, Department of Immunology and Virology.

105062, Moscow, Sadovaya-Chernogryazskaya str., 14/19, Phone: 7(916) 976-61-27

balnat07@rambler.ruЛазутоваА. А.LazutovaA. A.

Лазутова Анастасия Александровна — клинический ординатор.

Москва

 

Clinical Resident.

Moscow

balnat07@rambler.ruФГБУ «НМИЦ глазных болезней им. Гельмгольца» Министерства здравоохранения России, МоскваРоссияHelmholtz National Medical Research Center of Eye DiseasesRussian Federation202009122019222301310Copyright © Нероев В.В., Зайцева О.В., Балацкая Н.В., Лазутова А.А., 20202020Нероев В.В., Зайцева О.В., Балацкая Н.В., Лазутова А.А.Neroev V.V., Zaytseva O.V., Balatskaya N.V., Lazutova A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/1802

Диабетическая ретинопатия (ДР) имеет многофакторную природу с участием множества цитокинов и факторов роста. Изучение уровней цитокинов в биологических жидкостях представляется актуальным с целью углубленного понимания патогенеза заболевания. Цель работы — сравнительный анализ системных (сыворотка крови (СК)) и локальных (стекловидное тело (СТ)) уровней 45 цитокинов у пациентов с осложненной пролиферативной ДР, а также при различных особенностях клинической картины заболевания. Содержание цитокинов протестировано в 53 пробах СК и 32 пробах СТ 53 пациентов с сахарным диабетом 1-го и 2-го типа с тяжелым течением пролиферативной ДР. Использовали метод мультиплексного анализа на платформе хМАР в программе Luminex xPONENT 3.1, с помощью наборов 45 plex (ProcartaPlex, eBioscience, Австрия). В пределах уровней чувствительности тест-системы в значительном количестве тест-проб СК выявлялись 25, а СТ — 27 цитокинов. В пробах СТ средние уровни 7 медиаторов — IL-6, IL-8, IP-10, MCP-1, HGF, LIF и VEGF-A — оказались достоверно выше, чем в СК, что является доказательством их локальной интраокулярной продукции. Показаны корреляционные связи между содержанием в СТ ростового фактора VEGF-A и ряда цитокинов, в том числе участвующих в воспалительных реакциях, что свидетельствует о взаимосвязи звеньев патогенеза: воспаления и неоангиогенеза. Определены особенности интраокулярного содержания цитокинов при различных проявлениях диабетических изменений глаз. Показана связь гемофтальма с повышением IL-8 и IP-10, рубеоза радужки — с повышением LIF, активности пролиферативной ДР — с увеличением MCP-1, крайне тяжелых изменений — с ростом IL-6 и EGF. Тестирование цитокинов в биологических жидкостях информативно при изучении механизмов воспаления, неоангиогенеза, а также защитных реакций в патогенезе ДР.

Diabetic retinopathy (DR) is multifactorial by its origin, involving many cytokines and growth factors. Studies of cytokine levels in biological fluids seem to be relevant for an in-depth understanding of the disease pathogenesis. The purpose of the work was a comparative analysis of 45 cytokines at systemic (blood serum (BS)) and local (vitreous humor (VH)) levels in the patients with complicated proliferative DR, showing various features of the clinical pattern. The content of cytokines was tested in 53 samples of BS and 32 samples of VH in 53 patients with type 1 and type 2 diabetes mellitus with severe proliferative DR. We used the multiplex analysis technique by means of xMAP platform and Luminex xPONENT 3.1 program using 45-plex sets (Procarta Plex «eBioscience», Austria). 25 cytokines were detected at significant amounts in BS test samples, and 27 cytokines were revealed in VH specimens. Sensitivity limits of the test system allowed to find significantly higher levels of 7 cytokines (IL-6, IL-8, IP-10, MCP-1, HGF, LIF and VEGF-A) in VH samples, than in the BS, thus indicating to their local intraocular production. Correlations between the contents of VEGF-A growth factor and amounts of cytokines, including those involved in inflammatory reactions, are shown in VH, thus presuming the interrelation of pathogenetic components, i.e., inflammation and neoangiogenesis. The features of intraocular cytokine content were determined for various manifestations of diabetic ocular changes. Hemophthalmus has been shown to be associated with increased IL-8 and IP-10; iris rubeosis, with increase in LIF; proliferative DR activity was associated with higher MCP-1 levels, and extremely severe changes were related to increase in IL-6 and EGF. Testing of cytokines in biological fluids is informative when studying the mechanisms of inflammation, neoangiogenesis, and protective responses in pathogenesis of diabetic retinopathy.

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