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АНЕСТЕЗІОЛОГИ, ХІРУРГИ

International journal of endocrinology Том 17, №7, 2021

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Cytokines in the blood of patients with type 2 diabetes mellitus depending on the level of overweight/obesity (literature review and own data)

Authors: Зак К.П., Попова В.В., Орленко В.Л., Фурманова О.В., Тронько Н.Д.
ГУ «Институт эндокринологии и обмена веществ им. В.П. Комиссаренко НАМН Украины», г. Киев, Украина

Categories: Endocrinology

Sections: Specialist manual

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Summary

У роботі наведено аналіз сучасних даних літератури та результати власних досліджень щодо стану цитокінової мережі: про- та антизапальних цитокінів (інтерлейкіни (ІЛ) 1α, ІЛ-1β, ІЛ-4, ІЛ-6, ІЛ-10, ІЛ-17 та фактор некрозу пухлини альфа — ФНОα), α- та β-хемокінів, у тому числі ІЛ-8 та ІЛ-16, а також адипокінів (лептин та адипонектин) у периферичній крові хворих на цукровий діабет 2-го типу (ЦД-2) з нормальною та підвищеною масою тіла/ожирінням. Показано, що для хворих на ЦД-2 характерний підвищений вміст у периферичній крові прозапальних цитокінів (ІЛ-1, ІЛ-6, ІЛ-17, ФНПα) та α- і β-хемокінів, у тому числі ІЛ-8 та ІЛ-16, а також лептину при зниженні вмісту адипонектину. У худих хворих (індекс маси тіла (ІМТ) < 25,5 кг/м2) порівняно з худими нормоглікемічними особами контрольної групи (ІМТ < 25,5 кг/м2) відзначається невелике, але вірогідне підвищення ІЛ-1β, ІЛ-6, ІЛ-17, ФНПα та лептину, що в міру збільшення ІМТ значно зростає при вираженому ожирінні (ІМТ > 30,0 кг/м2), особливо у гладких жінок (ІМТ > 35,0 кг/м2). Аналогічно збільшення вмісту прозапальних цитокінів спостерігається і в нормоглікемічних людей, але не таке значне, як при ЦД-2. Менш чіткі дані були отримані при визначенні протизапальних цитокінів ІЛ-4 та ІЛ-10, що пояснюється значним поліморфізмом їх генів, як захисною, так і компенсаторною відповіддю на підйом рівня прозапальних цитокінів. У хворих на ЦД-2, особливо з ожирінням, спостерігається підвищений рівень лептину зі зниженням рівня адипонектину. Тяжкість перебігу та відсоток смертності тісно асоційовані з величиною ІМТ хворих. Боротьба зі збільшенням частоти захворюваності на ЦД-2 повинна бути в першу чергу спрямована на профілактику ожиріння, а при вже розвиненому захворюванні на ЦД-2 — на зниження супутнього ожиріння. Аналіз даних наводить також на думку, що різке підвищення вмісту прозапальних цитокінів («цитокіновий шторм»), що спостерігається у хворих на ЦД-2 та ожиріння, інфікованих COVID-19, є наслідком підсумовування та потенціювання вже наявного раніше запального процесу.

В работе приведены анализ современных данных литературы и результаты собственных исследований, касающихся состояния цитокиновой сети: про- и антивоспалительных цитокинов (интерлейкин (ИЛ) 1α, ИЛ-1β, ИЛ-4, ИЛ-6, ИЛ-10, ИЛ-17 и фактор некроза опухоли альфа — ФНОα), α- и β-хемокинов, в том числе ИЛ-8 и ИЛ-16, а также адипокинов (лептин и адипонектин) в периферической крови больных сахарным диабетом 2-го типа (СД-2) с нормальной и повышенной массой тела/ожирением. Показано, что для больных СД-2 характерно повышенное содержание в периферической крови провоспалительных цитокинов (ИЛ-1, ИЛ-6, ИЛ-17, ФНОα) и α- и β-хемокинов, в том числе ИЛ-8 и ИЛ-16, а также лептина при снижении содержания адипонектина. У худых больных (индекс массы тела (ИМТ) < 25,5 кг/м2) по сравнению с худыми нормогликемическими лицами контрольной группы (ИМТ < 25,5 кг/м2) отмечается небольшое, но достоверное повышение ИЛ-1β, ИЛ-6, ИЛ-17, ФНОα и лептина, которое по мере увеличения ИМТ значительно возрастает при выраженном ожирении (ИМТ > 30,0 кг/м2), особенно у тучных женщин (ИМТ > 35,0 кг/м2). Аналогично увеличение содержания провоспалительных цитокинов наблюдается и у нормогликемических людей, но не такое значительное, как при СД-2. Менее четкие данные были получены при определении антивоспалительных цитокинов ИЛ-4 и ИЛ-10, что объясняется значительным полиморфизмом их генов, как защитным, так и компенсаторным ответом на подъем уровня провоспалительных цитокинов. У больных СД-2, особенно с ожирением, наблюдается повышенный уровень лептина со снижением уровня адипонектина. Тяжесть течения и процент смертности тесно ассоциированы с величиной ИМТ больных. Борьба с увеличением частоты заболеваемости СД-2 должна быть в первую очередь направлена на профилактику ожирения, а при уже развившемся заболевании СД-2 — на снижение сопутствующего ожирения. Анализ приведенных данных наводит также на мысль, что резкое повышение содержания провоспалительных цитокинов («цитокиновый шторм»), наблюдаемое у больных СД-2 и ожирением, инфицированных COVID-19, является следствием суммирования и потенцирования уже имеющегося ранее воспалительного процесса.

The paper analyzes the current literature data and the results of our own researches concerning the state of the cytokine network: pro- and anti-inflammatory cytokines (interleukin (IL) 1α, IL-1β, IL-4, IL-6, IL-10, IL-17 and tumor necrosis factor (TNF) α), α- and β-chemokines, including IL-8 and IL-16, as well as adipokines (leptin and adiponectin) in the peripheral blood of patients with type 2 diabetes (T2D) with normal and increased body weight/obesity. It has been shown that patients with T2D are cha­racterized by an increased content of proinflammatory cytokines (IL-1, IL-6, IL-17, TNFα), α- and β-chemokines in the peripheral blood, including IL-8 and IL-16, as well as leptin with a decrease in adiponectin content. In lean patients (with body mass index (BMI) < 25.5 kg/m2) compared to lean normoglycemic individuals from the control group (BMI < 25.5 kg/m2), there is a small but significant increase in IL-1β, IL-6, IL-17, TNFα and leptin, which, as BMI increases, significantly increases in severe obesity (BMI > 30.0 kg/m2), especially in obese women (BMI > 35.0 kg/m2). Similarly, an increase in proinflammatory cytokines is observed in normoglycemic people, but not as signifi­cant as in T2D. Less clear data were obtained when during determination of the anti-inflammatory cytokines IL-4 and IL-10, which is explained by a significant polymorphism of their genes, and both protective and compensatory effects on pro-inflammatory cytokine rise. In T2D patients, especially those with obesity, there is an increase in the leptin level and a decrease in the adiponectin content. The severity of the course and the percentage of mortality are closely associated with the BMI of patients. The effectiveness of the fight against an increase in the incidence of T2D should be primarily aimed at preventing obesity, and in case of already developed T2D — at reducing concomitant obesity. The analysis of the data presented also suggests that a sharp increase in the content of pro-inflammatory cytokines (so called cytokine storm) observed in patients with T2D and obesity infected with COVID-19, is a consequence of the summation and potentiation of already existing inflammatory process.


Keywords

цукровий діабет 2-го типу; імунітет; цитокіни; COVID-19

сахарный диабет 2-го типа; иммунитет; цитокины; COVID-19

type 2 diabetes mellitus; immunity; cytokines; COVID-19


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