engleski

Effect of interleukin-18 on natural killer cell cytotoxic potential in patients with coronary heart disease during CABG

Introduction: Interleukin (IL)-18 is a co stimulatory factor in the activation of the pro- inflammatory immune response, acting on NK cells independently of IL-12 and IFN . It increases cytotoxicity mediated by the preformed perforin molecules. Perforin is the primary cytotoxic mediator, stored in granules of NK cells, which may be discharged to the stimulus. NK subtype of CD56 + dim phenotype with predominantly cytotoxic properties, and regulatory CD56 + bright NK subtype can kill after stimulation with IL-18. Ischemic heart disease in the background has a proinflammatory immune response, which is inherent with the activation of leukocyte subpopulations in peripheral blood, with possible damage of the coronary arteries and subsequent ischemic myocardial dysfunction. The aim of this study was to investigate the effect of IL-18 on perforin expression of NK cells in patients with coronary heart disease during surgical myocardial revascularization. Material and methods: Proportion of NK cells, the expression of IL18 receptor 1 (IL-18R1) and perforin were performed by immunofluorescence and flow cytometry, and the concentration of IL-18 was measured by ELISA using the leukocyte suspension, or sera prepared from blood samples from the aortic root (10 ml), coronary sinus (4 ml) and peripheral vena (10 ml) of patients with coronary artery disease at the moment of surgery, before connecting the patient to the machine for extra corporeal circulation. Samples of peripheral blood of healthy subjects served as a control group. Results: The concentration of IL-18 and the proportion of NK cells expressing the IL-18R1, was significantly higher in the peripheral blood of patients with coronary artery disease compared to healthy subjects and does not differ significantly from IL-18R1 expression in coronary circulation. Frequency of perforin expressing NK cells is lower in the peripheral blood of patients than healthy subjects and it is in negative correlation to the concentration of IL-18 in serum. The frequency of perforin positive NK cells in the coronary circulation did not differ significantly from the peripheral blood of patients, but was not directly correlated with IL-18. Conclusion: It is likely that IL-18 in the peripheral circulation activates NK cells by IL-18R1, which reduce the expression of perforin. In spite of the presence of IL-18 in the coronary circulation the frequency of perforin expressing NK cells did not decreased, probably due to the influence of immunostimulatory substances secreted by damaged, but a viable cardiomyocytes.

coronary artery disease; CABG; interleukin-18; perforin

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