The comparison of IL-17 levels in patients with unstable angina before and after medical treatment

1. Introduction

Interleukin-17 (IL-17) is one of the founders of an emerging family of inflammatory cytokines. IL-17 is produced almost exclusively by active T cells and is found mainly in the memory part of T cells [5, 6]. In contrast, its receptor is ubiquitous, and almost every cell will be a potential target for this cytokine [7]. In general, IL-17 receptor activation leads to the induction of other pro inflammatory cytokines through activation of nuclear factor-kB [8]. The allocation of IL-17 to specific subtypes has not yet been implemented. Recent studies have shown that IL-17 expression identifies a type of T-helper lineage that regulates tissue inflammation. Which supports the idea of a distinct effector lineage called “T(H)-17” [9]. However, previous studies have shown that IL-17 is activated by NK-specific T-CD4 + cell lines and belongs to the Th0, Th1, and Th2 subset [10], or vice versa, by some T1-CD4 + exclusively Th1/Th0 cells. Nor is it released from the Th2 type [11]. Thus, it is clear that the main role of IL-17 is to interact with the cytokine network, stimulate the secretion of inflammatory mediators, and thus establish a link between T cell activation and inflammation. IL-17 in inflammatory and autoimmune conditions including rheumatoid arthritis [13, 16, 17], inflammatory bowel disease [18], psoriasis [19], organ transplant rejection [20, 21], ischemic stroke [22] and Kawasaki disease [23] has been observed. Rheumatoid arthritis is of particular importance in terms of its association with atherosclerosis, in which failure to regulate cytokine production and chronic inflammation of synovial tissue in various joints is associated with an increased risk of atherosclerotic vascular disease [24, 25]. The morphological substrate of atherosclerosis is an atherosclerotic plaque, which prevents perfusion in the affected segment, contributes to reduction of coronary blood flow and leads to myocardial ischemia [1, 2, 3, 4, 5, 6]. In unstable angina, the duration of ischemia is insufficient to cause myocardial necrosis. Based on current data, the trigger mechanism of the pathogenesis of unstable angina is damage to the atherosclerotic plaque with thrombosis and episodes of spasm with subsequent progression of stenosis [1, 2, 7, 8, 9]. When an unstable plaque is damaged, after the rupture or erosion of the atherosclerotic plaque, coagulation factors interact with the thrombogenic content of the plaque, specifically collagen, thrombosis are developing. If the balance between prothrombotic and fibrinolytic mechanisms is unfavorable – occlusive blood clots are formed in this section of the vessel crease, which cause acute coronary syndromes, specifically unstable angina. The plaque vulnerability depends on the location, size and composition of the lipid nucleus, circular wall tension, the influence of blood flow on the surface of the atherosclerotic plaque (sher stress) [5, 6, 9, 10, 11]. If the balance is favorable, the blood clot is absorbed, at the site of the lesion there is a growth of connective tissue and calcification of the vascular wall, which, in turn, leads to deformation and stenosis of the vascular gap with consequential emergence of symptoms of stable angina [11]. It should be noted that the process of destabilizing the fibrous coating of the plaque, especially its rupture, is accompanied by activation of local inflammation. Pathomorphological researches indicate the presence of a large number of inflammatory cells, T-lymphocytes, monocytic macrophages on the place of rapture or on the surface of plaque erosion [4, 8, 12]. Endothelial dysfunction has a great role in the process of atherogenesis. It is an important cause of insufficient vasodilation and spasm of coronary arteries of different caliber [4]. To understand the processes that develop in an atherosclerotic altered vascular wall, it is important to study the markers of inflammation, since inflammatory processes play an important role in the formation and destabilization of atherosclerotic plaque. From inflammatory markers attract a much attention C-reactive protein (CRP), proinflammatory cytokines: interleukin-1 β (IL-1 β ) interleukin-6 (IL-6), interleukin-17 (IL-17), necrosis factor of alpha tumors (TNF-alpha) [13, 14, 15, 16]. The aim of our study is to evaluate and compare the IL-17 levels in unstable angina (UA) cases before and after treatment.

2. Methods

In this study, 48 UA patients, including 34 women and 16 men with a mean age of 56.60 years were included in the study (Tables 2 and 3). The mean serum level of interleukin 17 after treatment (65.13 ± 53.29 pg/dl) was significantly lower than its level before treatment (94.89 ± 51.25 pg/dL) ( 0/05). According to Table 1, the mean and standard deviation of the age of the studied patients was 60.56 ± 33.11 years, which varied from a minimum of 37 to a maximum of 83 years. According to Table 3, the mean and standard deviation of serum interleukin-17 levels before treatment in the studied patients was 94.89 ± 51.25 pg/dL, which varied from a minimum of 90.18 to a maximum of 80.151 pg/dl. According to Table 4, the mean and standard deviation of serum interleukin 17 after treatment in the studied patients was 65.13 ± 53.29 pg/dl, which varied from a minimum of 0.1 to a maximum of 109 pg/dl. According to Table 5, mean and standard deviation of serum interleukin 17 level after treatment was (65.13 ± 53.29 pg/dL) lower than serum interleukin 17 level before treatment (94.89 ± 51.25 pg/dL).

4. Discussion

Unstable angina and acute MI lead to acute coronary syndromes with a pathophysiological basis of thrombus formation on impaired atherosclerotic plaques [17]. Vulnerable plaques with thin fibrous caps with significant loss of extracellular matrix and thrombogenic nucleus are areas rich in inflammatory cells and therefore are the focus of inflammatory activity [18, 19]. An increase in the presence of inflammatory cells was observed in the lesions of UA patients compared with stable angina [20]. It was also observed in patients with unstable angina with complex coronary lesions compared with patients with simple lesions [21]. IL-17 is a proinflammatory cytokine with a specific role in chronic inflammatory conditions, the most prominent of which is rheumatoid arthritis [22, 23, 24]. The aim of this study was to compare the serum level of interleukin 17 in patients with unstable angina before and after drug treatment. In this study, 48 patients with unstable angina, including 34 women and 16 men with a mean age of 56.60 years were studied. The results showed that the mean serum level of interleukin 17 after treatment (13.65 ± 29.53 pg/dl) was significantly lower than its level before treatment (89.94 ± 25.51 pg/dl). All patients in the present study had high levels of interleukin 17 at the time of unstable angina. Previous authors, including Cheng et al, Liang et al. Jafarzadeh et al, and Zhang et al. reported high levels of interleukin-17 in patients with myocardial ischemia, including acute myocardial infarction and unstable angina [25, 26, 27]. Coronary artery atherosclerosis is a highly complex process in which many factors are involved. Interleukin 17 has been shown to play a very important role in the development and progression of atherosclerosis by affecting vascular smooth muscle cells [22]. Findings from previous studies and the present study also confirm the significant role of interleukin 17 in the pathogenesis of ischemic heart disease. According to the findings of the present study, the level of interleukin 17 significantly decreased one week after the patients’ drug treatment. Previous studies on this topic have been very limited, so that there was only a similar study conducted by Zhang et al. In 2017 [27]. They showed that interleukin 17 levels in patients with acute coronary syndrome (acute myocardial infarction and Unstable angina) has decreased after angioplasty treatment. The results of such studies indicate that interleukin 17 is considered as one of the influential factors in the inflammatory process in cardiovascular patients and is a suitable indicator for the diagnosis or treatment of such diseases. It is worth noting that none of the previous studies have studied the effect of medical therapy on reducing interleukin-17 levels, and this study is the first to address this issue and is unique in this regard. As to the limitations of the present study, firstly, the sample size of the experiment was small, secondly,the type of study did not allow us to draw conclusions on the direction of the association. Another possible pitfall was the lack of artery wall biopsy and subsequent culture of myofibroblasts to detect Il-17 tissue expression. Neither was adiposity evaluated by the more precise MRI, nor was arterial stiffness – judged by experts as a marker of asymptomatic atherosclerosis [28, 29, 30] – detected by means of pulse wave velocity.

5. Conclusion

In conclusion, these findings point towards a role of inflammation in the form of increased activity of IL-17 in patients of unstable angina and thus suggest that IL-17-driven inflammation may play a role in the promotion of clinical instability in patients with coronary artery disease.