Integral evaluation of the cytokine system in viral myocarditis

Abstract

The need for an individual approach in the choice of means for the prevention of complications in inflammatory processes in cardiomyocytes, the course of which unfolds against a persistent viral infection, dictates the need to determine the general mechanisms for maintaining and progressing of the pathological process and an objective evaluation of immunological changes. The aim of the study was to determine changes in the system of inflammatory mediators in patients with subacute and chronic herpesviral infectious myocarditis on the basis of an integral assessment of the levels of opposing groups of cytokines. Materials & methods. To achieve this goal, we conducted a determination and analysis of changes in the cytokine profile in 87 patients with subacute (from 2 to 6 months) and chronic (more than 6 months) myocarditis due to an integral assessment of the mediator levels of inflammation of opposing groups in patients with herpesviral myocarditis on treatment in medical institutions of the Kharkov city. The average age of the patients was (27 ± 7.4) years. The control group was attracted to 40 people without clinical manifestations of cardiovascular diseases and in whose anamnesis there were no data on the transferred inflammatory diseases of the myocardium. Both groups of subjects were comparable in age and gender. The main group of subjects was divided into two subgroups. The first was 44 patients with subacute flow, the second - 43 patients with chronic infectious myocarditis. The diagnosis was established in accordance with the recommendations of the Association of Cardiologists of Ukraine and experts of the European Society of Cardiology, according to the formation of definitions of diseases in the International Classification of Diseases (ICD-10) of the tenth revision. The removal of material from patients was carried out according to the rules for the collection of infectious material. The concentration of cytokines: IL-2, IL-4, IL-6, IL-10, INF-γ, TNF-α in serum was measured by enzyme-linked immunosorbent assay using commercial enzyme immunoassay kits for Thermo Scientific ™ (IL-2R IL-4, IL-6, IL-10, TNF alpha, IFN gamma ELISA Kit, Human, USA) and Stat Fax 303 Plus spectrophotometer. Statistical processing of all received data was carried out on a personal computer using the program Statistica, version 6.1 (StatSoft Inc., USA) [1]. Results & discussion. Analysis of levels of pro- and anti-inflammatory cytokines in patients indicates an imbalance in their system, which is characterized primarily by a significant increase in the level of IL-6 prophylaxis to (134.09 ± 22.72) pg / ml (control level 11.83 ± 1, 64 pg / ml) and a relatively moderate increase in IL-2 and TNF-α levels in subacute myocarditis. Such an increase in the level of IL-6, in our opinion, is due to the dualism of the action of this interleukin, the proinflammatory nature of its action at the final stage of inflammation changes to anti-inflammatory. As a consequence, in combination with IL-10, it limits the secretion of TNF-α. That is why its level remains high and with chronic herpesviral myocarditis and exceeds the level of the control group more than 8 times. In addition, in the chronic form of the course of herpesviral myocarditis, an increase in the levels of anti-inflammatory IL4 and IL-10 cytokines is observed in 2.9 and 3.1 times, respectively. And the level of IL-10 increased not only in comparison with the level of the control group, but also exceeded by 1.5 times the corresponding index for subacute myocarditis. In order to optimize the analysis of cytokine imbalance, an integral assessment of the levels of inflammatory mediators from opposing groups was carried out. Calculation of the integral indicator (II) of the cytokine balance was performed by determining the values of cytokine indices as the ratios of the levels of proinflammatory and anti-inflammatory sera in the examined patients to the reference values of the control group and the arithmetic mean for each opposing group of cytokines expressed in conventional units (c.u.). The optimal balance of cytokines corresponded to the level of II ≤ 1 c.u. and indicated the absence of inflammation, but the activity of the inflammatory process was characterized by exceeding the level of more than 1 condition. In the group of patients with subacute myocarditis, II was 6,27 c.u., exceeding the corresponding calculated indicator of a group of patients with chronic course in more than 1.6 times (3,82 c.u.). Therefore, the higher the deviation of the II from 1 cu is, the deeper the violation of immunological homeostasis. Conclusion.It was found that imbalance in the cytokine system in subacute and chronic herpesviral myocarditis is a universal immune system response, which is characterized by an increase in the levels of proinflammatory cytokines against a background of moderate growth of anti-inflammatory ones. The level of the integral cytokine index is more than 1 cu indicates the dysfunction of the immunological status of the patients being examined and can be used as an additional diagnostic criterion for the unfavorable course of the disease with a propensity to progress. Calculation of II defines a personalized diagnosis of cytokine imbalance with the ability to determine on its basis therapeutic approaches and the choice of immunorehabilitation tools, and also allows evaluating the effectiveness of selected anti-inflammatory agents for treatment of infectious herpesvirus myocarditis.