Резюме
Серік С.А. Про- та протизапальні цитокіни при серцевій недостатності у хворих на ІХС та цукровий діабет 2 типу зі збереженою фракцією викиду і систолічною дисфункцією лівого шлуночка.
У роботі проведене порівняння рівнів про- і протизапальних цитокінів у хворих на ішемічну хворобу серця з цукровим діабетом 2 типу і без нього при серцевій недостатності зі збереженою фракцією викиду і систолічною дисфункцією лівого шлуночка. У хворих на діабет, як і у хворих без діабету, при серцевій недостатності зі збереженою фракцією викиду лівого шлуночка виявлено достовірне підвищення фактору некрозу пухлин-α, інтерлейкінів-8 і -10, а формування систолічної дисфункції лівого шлуночка, на відміну від хворих без діабету, асоціювалось з подальшим зростанням тільки фактору некрозу пухлин-α. У хворих на діабет у порівнянні з хворими без діабету рівень фактору некрозу пухлин-α був більше і при збереженій фракції викиду, і при систолічній дисфункції лівого шлуночка, а рівень інтерлейкіну-10 - менше, але тільки при систолічній дисфункції лівого шлуночка.
Ключові слова: серцева недостатність, цитокіни, цукровий діабет 2 типу.
Резюме
Серик С.А. Про- и противовоспалительные цитокины при сердечной недостаточности у больных ИБС и сахарным диабетом 2 типа с сохраненной фракцией выброса и систолической дисфункцией левого желудочка.
В работе проведено сравнение уровней про- и противовоспалительных цитокинов у больных ишемической болезнью сердца с сахарным диабетом 2 типа и без него при сердечной недостаточности с сохраненной фракцией выброса и систолической дисфункцией левого желудочка. У больных диабетом, как и у больных без диабета, при сердечной недостаточности с сохраненной фракцией выброса левого желудочка выявлено достоверное повышение фактора некроза опухолей-α, интерлейкинов-8 и -10, а формирование систолической дисфункции левого желудочка, в отличие от больных без диабета, ассоциировалось с дальнейшим возрастанием только фактора некроза опухолей-α. У больных диабетом по сравнению с больными без диабета уровень фактора некроза опухолей-α был больше и при сохраненной фракции выброса, и при систолической дисфункции левого желудочка, а уровень интерлейкина-10 - меньше, но только при систолической дисфункции левого желудочка.
Ключевые слова: сердечная недостаточность, цитокины, сахарный диабет 2 типа.
Summary
Serik S.A. Pro- and anti-inflammatory cytokines in heart failure patients with ischemic heart disease and type 2 diabetes mellitus with preserved left ventricular ejection fraction and left ventricular systolic dysdunction.
The comparison of pro- and anti-inflammatory cytokines levels in heart failure patients with ischemic heart disease with and without type 2 diabetes mellitus with preserved left ventricular ejection fraction and left ventricular systolic dysdunction was performed in the study. In diabetics as well as non-diabetics with heart failure with preserved left ventricular ejection fraction the elevation of tumor necrosis factor-α, interleukins-8 and -10 levels was revealed, but as opposed to non-diabetics left ventricular systolic dysdunction formation was associated with further increase of tumor necrosis factor-α only. In diabetics tumor necrosis factor-α level was higher than in non-diabetics in heart failure with preserved left ventricular ejection fraction as well as in heart failure with left ventricular systolic dysdunction, and interleukin-10 level was lower, but only in heart failure with left ventricular systolic dysdunction.
Key words: heart failure, cytokines, type 2 diabetes mellitus.

Рецензент: д.мед.н., проф. Л.М. Іванова

УДК 616.12-008.46-092:616-005.4+616.379-008.64

ДУ «Національний інститут терапії імені Л.Т. Малої НАМН України» (Харків)

ГУ «Национальный институт терапии им. Л.Т. Малой НАМН Украины» (Харьков)

GI «L.T. Malaya Therapy National Institute of the NAMS of Ukraine» (Kharkiv)

shkapovl@gmail.com

Heart failure is characterized by systemic inflammatory response that contributes to development of many cardiac and extracardiac pathogenetic sequelae of this syndrome. Elevated levels of inflammatory cytokines, cytokine receptors, chemokines have been revealed in heart failure patients both with left ventricular systolic dysfunction and with preserved left ventricular ejection fraction. Circulating inflammatory mediators were found to correlate with heart failure disease severity and prognosis. Different diseases (ischemic heart disease (IHD), diabetes mellitus, hypertension etc.) lead to heart failure. Therefore, one of the key questions of the problem of immuno-inflammation in heart failure is whether immuno-inflammatory activation in heart failure is independent of the etiology or if there are disease specific mechanisms.

The aim of the study was the comparison of pro- and anti-inflammatory cytokines levels in heart failure patients with IHD with and without type 2 diabetes mellitus with preserved left ventricular ejection fraction and with left ventricular systolic dysfunction.

Methods.

73 patients with IHD with New York Heart Association functional class  II-IV of heart failure were examined. 35 patients had type 2 diabetes mellitus and 38 patients did not have diabetes (a mean age of (60,75±1,53) and (58,97±1,43) years respectively). The control group included 15 healthy persons in age of (47,27±1,92) years. According to left ventricular ejection fraction patients were divided into subgroups with preserved left ventricular ejection fraction (ejection fraction (EF) > 45 %) and with left ventricular systolic dysfunction (EF ≤ 45 %). Non-diabetics group included 19 patients with preserved left ventricular ejection fraction and 19 patients with left ventricular systolic dysfunction. Among diabetics 20 patients had preserved left ventricular ejection fraction and 15 patients had left ventricular systolic dysfunction. Proinflammatory cytokines (tumor necrosis factor-б (TNF-б), interleukin-8 (IL‑8) and anti-inflammatory cytokine interleukin-10 (IL-10) were measured in serum by commercially enzyme-linked immunosorbent assay kits.

Results.

In patients without diabetes with preserved left ventricular ejection fraction the serum levels of both proinflammatory cytokines TNF-б and IL-8, as well as anti-inflammatory cytokine IL-10 were significantly higher than in control group. In non-diabetics with left ventricular systolic dysfunction TNF-б, IL-8 and IL-10 levels were augmented in comparison to patients with preserved left ventricular ejection fraction (table 1).

Table 1.

TNF-б, IL-8 and IL-10 levels in patients with IHD without diabetes in heart failure with preserved left ventricular ejection fraction and with left ventricular systolic dysfunction.

Note. р is statistical significance of differences with pointing of the compared groups.

In patients with type 2 diabetes mellitus with preserved left ventricular ejection fraction TNF-б, IL-8 and IL-10 serum levels were significantly increased compared to control group. In patients with diabetes with left ventricular systolic dysfunction TNF-б level were higher than in patients with preserved left ventricular ejection fraction. The increase of IL-8 and IL-10 levels in diabetic patients with left ventricular systolic dysfunction in comparison with patients with preserved left ventricular ejection fraction was insignificant (table 2).

Table 2.

TNF-б, IL-8 and IL-10 levels in patients with IHD with type 2 diabetes mellitus in heart failure with preserved left ventricular ejection fraction and with left ventricular systolic dysfunction.

Note. р is statistical significance of differences with pointing of the compared groups.

The comparison of cytokines levels in diabetic and non-diabetic patients with heart failure with preserved ejection fraction revealed that in patients with diabetes TNF-б level was significantly higher than in patients without diabetes (p<0,05) while IL-8 and IL-10 levels did not differ. In patients with left ventricular systolic dysfunction TNF-б level was also higher in diabetics than in non-diabetics (p<0,01) and there was no significant difference in IL-8 level. The level of anti-inflammatory cytokine IL-10 in patients with left ventricular systolic dysfunction with diabetes was significantly lower than in patients without diabetes (p<0,05).

Thus, in diabetics as well as non-diabetics with heart failure with preserved left ventricular ejection fraction the elevation of TNF-б, IL-8 and IL‑10 levels was revealed, but as opposed to non-diabetics left ventricular systolic dysfunction formation was associated with further increase of TNF-б only. In diabetics TNF‑б level was higher than in non-diabetics in heart failure with preserved left ventricular ejection fraction as well as in heart failure with left ventricular systolic dysfunction, and IL-10 level was lower, but only in heart failure with left ventricular systolic dysfunction. Overall, the results of the comparison of pro- and anti-inflammatory cytokines activity in heart failure patients with and without diabetes can be considered as indirect evidence that the inflammatory activation in heart failure in patients with type 2 diabetes mellitus has specific features of the development and pathogenetic significance.

Conclusions

1. In patients with IHD without diabetes in heart failure with preserved left ventricular ejection fraction the significant elevation of proinflammatory (TNF-б, IL-8) and anti-inflammatory (IL-10) cytokines is observed. Heart failure with left ventricular systolic dysfunction in these patients is characterized by the greater activation of the inflammatory mediators.
2. In patients with IHD and with type 2 diabetes mellitus in heart failure with preserved left ventricular ejection fraction as well as in non-diabetics TNF‑б, IL-8 and IL-10 levels increase. But as opposed to non-diabetics in heart failure with left ventricular systolic dysfunction as compared with heart failure with preserved left ventricular ejection fraction the increase of TNF-б level is revealed only.
3. In diabetic patients with IHD in comparison with non-diabetics in heart failure both with preserved left ventricular ejection fraction and with left ventricular systolic dysfunction TNF-б levels elevate in more degree while the differences in IL-8 levels are not significant. In diabetics and non-diabetics with heart failure with preserved left ventricular ejection fraction anti-inflammatory cytokine IL-10 levels rise equally, but in heart failure with left ventricular systolic dysfunction in patients with diabetes IL-10 level increases significantly less than in patients without diabetes.

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