rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2018-697-702rsp-2644Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHАдипоцитокины при раннем ревматоидном артрите: взаимосвязь с про- и антивоспалительными маркерамиAdipocytokines in early rheumatoid arthritis: relationship to pro- and anti-inflammatory markersКондратьеваЛ. В.KondratyevaL. V.kondratyeva.liubov@yandex.ruПопковаТ. В.PopkovaT. V.ГорбуноваЮ. Н.GorbunovaYu. N.ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой».РоссияV.A. Nasonova Research Institute of Rheumatology.Russian Federation201821012019566697702Copyright © Кондратьева Л.В., Попкова Т.В., Горбунова Ю.Н., 20192019Кондратьева Л.В., Попкова Т.В., Горбунова Ю.Н.Kondratyeva L.V., Popkova T.V., Gorbunova Y.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/2644

Цель исследования – уточнить взаимосвязь адипонектина и лептина с показателями активности заболевания и уровнями про- и антивоспалительных цитокинов у больных с ранним ревматоидным артритом (РА).Материал и методы. В исследование включены 27 больных РА, соответствующих критериям ACR/EULAR 2010 г., никогда не получавших глюкокортикоиды (ГК) или базисные противовоспалительные препараты. Медиана возраста пациентов составила 56 [46; 64] лет, длительности заболевания – 8 [6; 15] мес. Все больные имели умеренную или высокую активность РА по индексу DAS28. Большинство были серопозитивными по ревматоидному фактору – 88,9% и антителам к циклическому цитруллинированному пептиду – 96,3%. В контрольную группу вошли 30 человек без воспалительных заболеваний суставов, сходных по полу, возрасту и индексу массы тела (ИМТ) с больными РА. Концентрации адипонектина и лептина определяли с помощью иммуноферментного анализа, для измерения концентрации интерлейкина 1β (ИЛ1β), ИЛ2, ИЛ4, ИЛ5, ИЛ6, ИЛ7, ИЛ8, ИЛ9, ИЛ10, ИЛ12, ИЛ13, ИЛ15, ИЛ17 и макрофагальных белков воспаления (MIP) – MIP1α, MIP1β – применялась мультиплексная технология X-MAP.Результаты и обсуждение. У больных РА концентрация адипонектина оказалась выше (р<0,001), а содержание лептина и соотношение лептин/адипонектин (Л/А) – ниже, чем в контроле (p=0,04 и р<0,001 соответственно). При РА обнаружены прямые корреляции уровня лептина с ИЛ17 (r=0,4; p=0,03), ИЛ4 (r=0,39; p=0,04) и скоростью оседания эритроцитов (СОЭ; r=0,3; p=0,05), а также отношения Л/А с СОЭ (r=0,38; p=0,05), уровнями СРБ (r=0,4; p=0,04) и MIP1β (r=0,55; p=0,03). Нарастание концентрации адипонектина ассоциировалось со снижением содержания MIP1β (r=-0,63; p<0,01). У лиц с ИМТ ≥25 кг/м2 концентрации лептина при РА и в контроле оказались сопоставимы (р=0,1), различия в содержании адипонектина и в отношении Л/А сохранялись (р<0,001 в обоих случаях). В данной подгруппе у пациентов с РА оставались значимыми корреляции между уровнями лептина и ИЛ17 (r=0,52; p=0,03), концентрациями адипонектина и MIP1β (r=-0,59; p=0,01), отношением Л/А и содержанием MIP1β (r=0,55; p=0,02).Заключение. При раннем РА снижается синтез лептина и увеличивается продукция адипонектина. Корреляции между уровнями адипоцитокинов и ИЛ17, MIP1β, с одной стороны, свидетельствуют о влиянии жировой ткани на системное воспаление, с другой – подтверждают участие провоспалительных цитокинов в развитии инсулинорезистентности и ожирения.

Objective: to clarify the relationship of adiponectin and leptin to the signs of disease activity and the levels of pro- and anti-inflammatory cytokines in patients with early rheumatoid arthritis (RA).Subjects and methods. The investigation enrolled 27 RA patients who met the 2010 ACR/EULAR classification criteria and had never received glucocorticoids (GCs) or disease-modifying antirheumatic drugs. The median age of the patients was 56 [46; 64] years; the duration of the disease was 8 [6; 15] months. All the patients had moderate or high RA activity according to DAS28. The majority of the patients were seropositive for rheumatoid factor (88.9%) or anticyclic citrullinated peptide antibodies (96.3%). A control group included 30 gender-, age-, and body mass index (BMI)-matched people without inflammatory arthritis. Enzyme immunoassay was used to estimate the concentrations of adiponectin and leptin; XMAP multiplex assay was applied to measure the levels of interleukin-1β (IL-1β), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17 and macrophage inflammation proteins (MIP), such as MIP-1α and MIP-1β.Results and discussion. In RA patients, adiponectin concentrations were higher (p<0.001) and leptin levels and leptin/adiponectin (L/A) ratios were lower than those in the controls (p=0.04 and p<0.001, respectively). In RA, there were direct correlations of leptin levels with concentration of IL-17 (r=0.4; p=0.03), IL-4 (r=0.39; p=0.04) and erythrocyte sedimentation rate (ESR) (r=0.3; p=0.05), as well as relationships of L/A ratios to ESR (r=0.38; p=0.05) and the levels of CRP (r=0.4; p=0.04) and MIP-1β (r=0.55; p=0.03). An increase in adiponectin concentrations was associated with a decrease in MIP-1β levels (r=-0.63; p<0.01). In patients with BMI ≥25 kg/m2, leptin concentrations were comparable in RA patients and controls (p=0.1); the differences in adiponectin levels and L/A ratios remained in both cases (p<0.001). This subgroup of patients with RA showed significant correlations between leptin and IL-17 levels (r=0.52; p=0.03), adiponectin and MIP-1β concentrations (r=-0.59; p=0.01), L/A ratios and MIP-1β levels (r=0.55; p=0.02).Conclusion. In early RA, there was a lower leptin synthesis and a higher adiponectin production. The correlations between the levels of adipocytokines, IL-17, and MIP1β, on the one hand, suggest that adipose tissue has an impact on systemic inflammation and, on the other, confirm that proinflammatory cytokines are involved in the development of insulin resistance and obesity.

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