IMMUNOPATHOGENESIS OF HEART FAILURE IN PATIENTS WITH INFECTIVE-IMMUNE MYOCARDITIS

Abstract

Aim. To study quantitative parameters, specifics of functional state of the main subpopulations of peripheral blood lymphocytes of the infective-immune myocarditis patients (IIM) and postmyocarditis cardiosclerosis (PMC), and specifics of cytokine profile.Material and methods. Totally, 35 IIM patients included, and 39 with PMC. In 17 patients with IIM there was significant heart failure (HF) — III functional class (FC) by New-York Heart Association (NYHA), in 18 patients with IIM there were no signs of HF, or mild signs (0-II FC by NYHA). In 18 patients with PMC there were no signs of HF, and in 21 — there was I FC by NYHA. The controls were 10 formally healthy persons. Study of population and subpopulation contents, and lymphocytes activation markers of peripheral blood, was done with four-color laser flow cytometry using FACSCalibur equipment and relevant monoclonal antibodies (Beckton Dickinson, USA). We studied the mean cytokines concentrations characterizing Th1-, Th2- and Th17- subpopulations of the helper lymphocytes. Measurement of serum cytokines was done with the method solid-phase immune-enzyme assay with LLC “Vectro-Best” (Russia) media. Statistics was done with software PASW Statistics 18.Results. Inflammatory diseases of myocardium show the deviations of native, as acquired immunity. In IIM and PMC there was significant decrease of NKTlymphocytes, not related to the severity of HF signs and durations of the disease. Immunity activation signs in IIM group showed the increase of the early activator marker CD25 expression activation, that was marked during the first 2 weeks from the disease onset. Following, by the end of the 1st month and on the 2nd month from the disease onset, the increase of T- and non-T-lymphocytes was found with the signs of delayed activation, revealed by HLA-DR antigen expression. The activator marker patterns were differ in patients with different grade of HF severity. Concentration of interferon-γ (IFN-γ) and interleukine (IL)-4 was more than 3 times higher in IIM patients comparing to controls. There was more than 7-times higher increase of IL-17A, and concentrations of effectory cytokines of Th17-subpopulation — IL-8 and granulocyte-macrophagal colony-stimulating factor (GM CSF). The level of IFN-γ reached maximal levels during the first 2 weeks from the disease onset. Later, IFN-γ concentration declined. Opposite, serum level of IL-4 was significantly increased by the end of the 1st and on the 2nd month from disease onset. Concentrations of IL-17A, IL-8 and GM CSF in blood serum were increased during the whole 2nd week, by the end of the 1st month and on the 2nd month. Th17-cytokines concentrations were significantly increased in PMC patients. Level of IL-17A was higher than in controls almost two times, IL8 — by 51%, GM CSF — by 50%. Serum levels of IL-4, and IL-17A, IL-8 and GM CSF were higher in subgroup of PMC patients with the disease duration less than 6 months. Conclusion. Disorders of anti-infection immunity and mechanisms of selfrestriction of immune reactions do play important role in development of myocardium damage of inflammatory origin.

Keywords

• infective-immune myocarditis
• postmyocarditis cardiosclerosis
• lymphocytes
• immune activation