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THE ROLE OF CYTOKINE SPECTRUM IN CHILDREN WITH CARDIOMYOPATHY
Akhmedova Dilorom Ilhamovna, director, of the Republican Specialized Scientific and Practical Medical Center of Pediatrics Akhmedova Nilufar Rasulovna, doctoral, student of Tashkent Pediatric Medical Institute
The Republic of Uzbekistan E-mail: evovision@bk.ru
THE ROLE OF CYTOKINE SPECTRUM IN CHILDREN WITH CARDIOMYOPATHY
Abstract: Cytokines play an important role in the progression of heart failure in children with cardiomyopathy in children. The severity of their shifts is determined by the degree of circulatory disturbance, its duration, does not depend on the etiologic factor of heart failure and determines the prognosis of the disease. Keywords. Children, cardiomyopathy, cytokines, tumor necrosis factor.
The immune system is one of the most important integrating systems responsible for maintaining the homeostasis and viability of the child's organism in various environmental conditions. At present, there is no doubt that it plays a leading role in the pathogenesis, clinical course and outcome of cardiovascular diseases in children caused by metabolic disorders.
The reason for the high incidence of an unfavorable outcome in these pathological conditions is a combination of severe vascular circulatory disorders, a systemic inflammatory reaction accompanied by cytokine assault, disrupting metabolic and hemodynamic processes in the body.
The effect of cytokines on the clinical picture and the course of cardiovascular diseases in children is effected through effects on the immune, central nervous and endocrine systems. In recent years, among a large number of studied inflammatory response markers, researchers focus on interleukins and tumor necrosis factor-a (TNF-a), which are very sensitive markers.
All of the above indicates the relevance of the study of proinflammatory immunocytokines and the activation-pro-liferative link of immunological response in children with cardiomyopathies.
Purpose of the study. To study the effects of cytokines (tumor necrosis factor TNF-a and IL-1, IL-6 and IL-8) on the clinical course of cardiomyopathies in children.
Materials and methods. 104 children were hospitalized in the cardiorheumatological departments of the RSNPMC Pediatrics in Tashkent and the RDMMC in Karakalpakia and 20 practically healthy children (control group). The age of the examined children ranged from 2 to 17 years and averaged 8.9 ± 0.6 years.
The diagnosis was made on the basis of complaints, objective examination, laboratory and instrumental methods of investigation (clinical and biochemical blood tests, chest X-ray, ECG and Echocardiogram of the heart). We examined immune methods of investigation, including the determination of TNF-a and IL-1, IL-6 and IL-8 using standard test systems for the ELISA OOO "Cytokine" (St. Petersburg). The studies were carried out in the clinical and laboratory department of the RSNPMC of pediatrics (headed by Prof. AN Aripov).
Hypertrophic cardiomyopathy (HCMC) was diagnosed in 45.2%, dilated cardiomyopathy (DCM) - in 42.3% and restrictive (RCMP) form - in 12.5% of children.
Results and discussion. Attention is drawn to the ambiguous effect of circulatory insufficiency and hypoxia on the ability of children to produce TNF-a. So, if mild hypoxia is accompanied by a significant increase in the level of TNF-a in the blood serum, in the case of severe hypoxia in these children, its level was reduced.
Table 1.- Comparative characteristics content in different stages of circulatory disorders in children with cardiomyopathies
Stages TNF-a, pg / ml IL -1, pg / ml IL-6, pg / ml IL-6, pg / ml
Control 27.3 ± 2.55 2.3 ± 0.5 6.0 ± 0.8 6.8 ± 0.7
DCM CD I ct. 12.6 ± 0.4*** 1.5 ± 0.3 6.8 ± 1.4 7.8 ± 1.1
DCM CD IIA ct. 11.5 ± 0.3*** 1.6 ± 0.4 21.7 ± 1.8*** 7.2 ± 0.9
DCM CD IIB-III ct 6.9 ± 0.2*** 2.9 ± 0.2* 30.7 ± 4.3*** 9.8 ± 1.2
HCMP CD I ct. 11.9 ± 0.4*** 1.9 ± 0.4 9.88 ± 0.6*** 7.1 ± 0.4
HCMP CD IIA ct. 9.8 ± 0.4*** 2.8 ± 0.4* 14.75 ± 0.6*** 8.6 ± 0.7
Note: * - the differences with respect to the control group are significant (* - P < 0.05, ** - P < 0.01, *** - P < 0.001)
Section 11. Medicine
The conducted immunogenetic studies indicated that if moderate hypoxia is accompanied by a significant increase in serum TNF-a level, then in the case of severe hypoxia in these children, its level was lowered.
With different degrees of circulatory failure, the level of TNF-a has its own characteristics. So, both in DCM and HCMP, the lower the level of TNF-a than the circulatory insufficiency. A more pronounced decrease in TNF-a is observed with DCM NK IIB-III st. In a comparative aspect with CD1 st degree and IIA st. the level of TNF-a is significantly higher in children with DCM than in children with HCMP.
Comparative analysis of the content of antiinflammatory interleukins in patients with cardiomyopathies, revealed the existence of an interrelation between the level of cytokines and the degree of circulatory disturbance, i.e. We observed pronounced changes in the production of IL-1, IL-6 and IL-8, depending on the stage of the CD.
A slight hyperproduction of TNF-a, IL-1 in patients with CD IIB-III st. with DCM and with CD II st. n IL-6 and IL-8 in the stage of CD IIA st. and the expressed stage of CD IIB-III st. with DCM.
As we showed earlier, the increase in production ofIL-1 and IL-6 may be one of the reasons for the increased synthesis of TNF-a in such patients. In this case, TNF-a can be considered as an autocrine accessory of myocardial dysfunction in hypoxic states. TNF-a, IL-1, IL-6 can play an important role in the realization of hypercoagulation processes, disturbance of vascular tone regulation, and the formation of endothelial dysfunction [1,2]. The reason for the increase in the content of these cytokines is systemic hypoxia and inflammatory syndrome, manifested in the last stages of heart failure with a deep microcirculation defect.
The correlation analysis of the serum content of the cyto-kines studied showed a close correlation dependence of their
concentrations on the degree of echocardiographic changes in the heart. In children with DCM, the degree of LV dilatation was determined from the level of IL-1 and IL-8: the final diastolic size (CDR) of IL-1 concentration (KDR-IL-1, r = 0.52, p < 0.05); of the final diastolic volume (BWW) from the level of IL-8 (BDO-IL-8, r = 0.57, p < 0.05). An inverse relationship was established between the parameter of the ejection fraction and IL-6 (r = -0.48). A decrease in the ratio of the amplitude of early and late LV filling (V1/V2), indicative of diastolic dysfunction, was also associated with an increase in the level of IL-8 (V1 / V2-IL-8, r = 0.59, p < 0.05). In patients with NK IIB-III st. The dependence of the content of troponin I on the concentration of IL-6 (r = 0.54, respectively, p < 0.05) was noted. The results obtained confirm that cytokines play an important role in the progression of heart failure. The severity of these shifts is determined by the degree of circulatory disturbance, its duration, does not depend on the etiologic factor of heart failure and determines the prognosis of the disease.
Conclusions:
1. With CML in children, the greater the circulatory failure, the lower the level of TNF-a. A more pronounced decrease in TNF-a was observed with DCM DC IIB-III st.
2. In children with dilated cardiomyopathy, the degree of LV dilatation is directly related to the level of IL-1 and IL-8: the final diastolic size (CDR) of IL-1 concentration (KDR-IL-1, r = 0.52); of the final diastolic volume (BWW) from the level ofIL-8 (BWO-IL-8, r = 0.57) and the inverse relationship between the parameter of the ejection fraction and IL-6, (r = -0.48).
3. The level of proinflammatory interleukins in patients with cardiomyopathies depends on the degree of circulatory disturbance and the production of IL-1, IL-6 and IL-8 varies depending on the stage of the ND.
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