|Year : 2014 | Volume
| Issue : 2 | Page : 80-83
Serum levels of interleukin-17 in patients with and without acute coronary syndrome: A cross-sectional study in Babol, Northern Iran
Mehrdad Saravi1, Afshin Khani2, Ghorban Maliji3, Mohammad Khalili4, Seyedeh Khadijeh Dariabory1, Zahra Sheikh4
1 Department of Cardiovascular Diseases, Babol University of Medical Sciences, Babol, Iran
2 Student Research Committee; Cellular and Molecular Biology Research Center, Babol University of Medical Sciences, Babol, Iran
3 Cellular and Molecular Biology Research Center; Department of Immunology, Babol University of Medical Sciences, Babol, Iran
4 Student Research Committee, Babol University of Medical Sciences, Babol, Iran
|Date of Web Publication||3-Oct-2014|
Ayatollah Roohani Hospital, Babol University of Medical Sciences, Ganjafruz Street, Babol
Source of Support: The Deputy of Research of Babol University of Medical Sciences for the financial support, Conflict of Interest: None
Background: The role of interleukin-17 (IL-17) in patients with acute coronary syndrome (ACS) is controversial.
Objective: The aim of this study was to assess the serum level of IL-17 in patients with acute myocardial infarction (AMI) and unstable angina (UA) in Babol, Northern Iran in 2012.
Materials and Methods: A total of 60 patients with ACS (30 with AMI, 30 with UA) and 30 healthy blood donors of Babol city, Iran were recruited in this cross-sectional study. Simple sampling method was used for patient selection. The inclusion criteria were the recent (<48 h) diagnosis of AMI or UA. The exclusion criteria were: Diagnosis of AMI or UA >48 h, recent history of infection or use of antibiotics. The serum IL-17 level was measured using enzyme-linked immunosorbent assay kit (Bioscience, Texas, USA). The lowest concentration of IL-17 that the kit could detect was 0.8 pg/ml. Chi-square, and Kruskal-Wallis tests were used for the comparison of IL-17 level between participants. P < 0.05 was considered as significant.
Results: A total of 10 participants were excluded due to contaminated blood samples. Fifty (62.5%) were males and 30 (37.5%) were females. Four (13.3%) patients of AMI group and 1 (3.3%) of UA group had detectable levels of IL-17 (P = 0.353), but no one in blood donors (P = 0.114). There was also no significant association between the presence of detectable level of IL-17 and history of diabetes mellitus, hypertension, hyperlipidemia, smoking (P > 0.05).
Conclusion: Our study did not find any significant differences in the serum level of IL-17 in individuals with or without ACS and therefore did not support the theory in which IL-17 has deleterious role in atherosclerosis.
Keywords: Acute coronary syndrome, blood, interleukin-17, myocardial infarction, unstable angina
|How to cite this article:|
Saravi M, Khani A, Maliji G, Khalili M, Dariabory SK, Sheikh Z. Serum levels of interleukin-17 in patients with and without acute coronary syndrome: A cross-sectional study in Babol, Northern Iran. Nig J Cardiol 2014;11:80-3
|How to cite this URL:|
Saravi M, Khani A, Maliji G, Khalili M, Dariabory SK, Sheikh Z. Serum levels of interleukin-17 in patients with and without acute coronary syndrome: A cross-sectional study in Babol, Northern Iran. Nig J Cardiol [serial online] 2014 [cited 2021 Jul 24];11:80-3. Available from: https://www.nigjcardiol.org/text.asp?2014/11/2/80/142086
| Introduction|| |
Acute coronary syndrome (ACS) is one of the major causes of morbidity and mortality worldwide. , The syndrome has two major clinical presentations including unstable angina (UA) and acute myocardial infarction (AMI). Despite proposing several mechanisms for describing the pathophysiology of ACS, the exact mechanism is still unknown. Among the presumptive mechanisms, growing body of literature has emerged the role of inflammatory and immunopathological reactions in the formation of an atherosclerotic plaque. ,, It seems that both innate and adaptive immune systems are involved in the inflammation, erosion and rapture of the atherosclerotic plaque.  According to this hypothesis, many researchers have conducted studies with the aim of identifying cytokines and their roles in the process of atherosclerosis. 
Among the various cytokines that have been discovered to date, the role of the recent described cytokine interleukin-17 (IL-17) in atherosclerosis is controversial. , IL-17 is a pro-inflammatory cytokine. The main source of its secretion is type 17 helper T (Th17) cells, a new described linage of CD4 + T-cells. , However, it has been shown that IL-17 is also secreted by other hematopoietic cells such as natural killer T-cells, macrophages, dendritic cells, neutrophils and mast cells.  The main target cells for IL-17 are epithelial cells, endothelial cells, fibroblasts and macrophages and dendritic cells.  Previous studies on the role of IL-17 addressed its presumptive role in the pathophysiology of immune-mediated diseases, such as rheumatoid arthritis, psoriasis, colitis and asthma.
The role of IL-17 in the arthrosclerosis is thought to be from the activation of downstream signaling pathways by IL-17 such as nuclear factor-κB, chemokines (CXCL1, CXCL5, IL-8, CCL2 and CCL7), and matrix metalloproteinase. , Also, IL-17 has been shown to be involved in the recruiting of neutrophils to the inflammatory site.  As a result, majority of previous studies has tended to focus on deleterious role of IL-17 in atherosclerosis. On the other hand, recent evidence showed contradictory findings and emerged protective role of IL-17 in atherosclerosis. For example, recent experimental studies reported mice with T-cell deficient for suppressor of cytokine signaling displayed higher levels of IL-17 and reduced atherosclerotic lesion size.  Moreover, it was shown that plaque stability was associated with elevated expression of IL-17 in human carotid lesions.  However, few clinical studies have assessed these hypothetical roles and there are no enough data for determining the role of IL-17 in patients with ACS. Thus, the aim of this study was to assess the serum level of IL-17 in patients with AMI and UA in Babol, Northern Iran in 2012.
| Materials and methods|| |
Study design and patient selection
Sixty patients with ACS (30 with AMI and 30 with UA) and 30 healthy blood donors of Babol city, Iran from October 2012 to October 2013 were recruited in this cross-sectional study. Simple sampling method was used for patient selection. The inclusion criteria were the recent (<48 h) diagnosis of AMI or UA. The diagnosis of MI was made according to presences of two of three following criteria: Symptoms of ischemia, electrocardiographic changes (ST-segment elevation >1 mm in two contiguous lead) and rise of cardiac biomarkers (cardiac troponin and creatine kinase MB). UA was defined as the presence of ischemic symptoms suggestive of an ACS without elevation in cardiac biomarkers with or without electrocardiogram changes indicative of ischemia. The exclusion criteria were: Diagnosis of AMI or UA >48 h ago, recent history of infection, recent use of antibiotics and missed blood samples. The demographic data, history of smoking, use of anti-hypertensive and anti-dyslipidemic agents were asked from all patients. The Local Ethics Committee of Babol University of Medical Sciences approved the protocol of the study and informed consent was obtained from the study population.
Blood sampling and interleukin-17 measurement
Peripheral blood samples (5 ml) were collected from all participants. The samples were transported to the Laboratory of Molecular and Cellular Research Center affiliated to the Babol University of Medical Sciences. The serum was separated and stored at −80°C. The serum IL-17 level was measured using the commercial enzyme-linked immunosorbent assay kit (Bioscience, Texas, USA). The lowest concentration of IL-17 that the kit could detect was 0.8 pg/ml.
The data were analyzed using SPSS software version 16 (IBM Corporation, New York, United States). Kolmogrov-Smirnove test was used for testing the normal distribution of quantitative variables. A Chi-square, Fisher's exact and Kruskal-Wallis tests were used for the comparison of IL-17 level between participants. P < 0.05 was considered as significant.
| Results|| |
Of the 90 individuals enrolled in this study, 10 participants were excluded due to contaminated blood samples. From the remaining 80 participants, 50 (62.5%) were males and 30 (37.5%) were females. The mean age of participants was 55.73 ± 13.97 years. Of 60 patients within AMI and UA groups, 7 (11.7%) were smokers, 24 (40%) had diabetes mellitus (DM), 14 (23.7%) dyslipidemia and 42 (70%) with hypertension (HTN). The baseline variables of patients with ACS were shown in [Table 1]. In the blood donors group, 12 (60%) subjects were males and 8 (40%) were females and their mean age was 45.84 ± 5.49 years.
Serum level of interleukin-17
The detectable level of IL-17 was observed in 4 (13.3%) patients of AMI group and 1 (3.3%) of UA group (P = 0.353). There were no individuals with detectable level of IL-17 in the blood donors group. There were no significant associations between the presence of detectable level of IL-17 and three groups (P = 0.114). There were also no significant associations between the presence of detectable level of IL-17 and history of DM, HTN, hyperlipidemia, smoking (P > 0.05) [Table 2]. The mean level of IL-17 in patients with detectable level was 3.581 pg/ml. The mean level of IL-17 in AMI and UA patients with detectable level was 3.483 pg/ml and 3.974 pg/ml, respectively (P > 0.05). The level of IL-17 in all patients is shown in [Figure 1].
|Figure 1: Mean ± SE serum concentration of interleukin-17 in acute myocardial infarction and unstable angina group (P = 0.165)|
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|Table 2: Frequency of detectable IL-17 level according to the presence of traditional IHD risk factors|
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| Discussion|| |
In the current study, the proportion of patients with detectable serum level of IL-17 and the mean serum level of IL-17 was higher in patients with ACS compared with healthy blood donors. However, this difference has not been reached to a statistically significant level. Furthermore, this study failed to show any significant differences between the serum levels of IL-17 in patients with AMI in comparison to UA.
There are few studies in which the association of IL-17 and different presentations of ACS were investigated. In a similar study, Jafarzadeh et al. compared the circulating levels of IL-17 in patients with AMI, UA, and healthy blood donors. The authors reported that the mean level of IL-17 is significantly higher in AMI and UA groups compared with healthy blood donors. However, they reported no significant differences between AMI and UA groups.  Another study by Damås et al. demonstrated that serum levels of IL-17 are significantly higher in both stable and UA patients compared with the healthy blood donors. Of note, this study reported significantly higher levels of IL-17 in UA group compared to the stable angina group. The authors of this study suggest that platelets are one of the major sources of IL-17 levels in plasma. 
In contrast to the mentioned studies, another set of data did not support the deleterious role of IL-17 in atherosclerosis. Eid et al. in their study found no significant differences in the serum level of IL-17 in patients with or without coronary artery disease.  Moreover, the study of Simon et al. showed that high serum IL-17 levels are associated with better long-time outcome in patients with AMI and therefore, they suggested a regulatory role for IL-17 in coronary heart disease. 
There are different theories for both deleterious and regulatory role of IL-17 in atherosclerosis. The expression of IL-17 in atherosclerotic plaque and inducing the production of pro-inflammatory mediators and vascular cell adhesion molecule-1 (VCAM-1) is believed to play a role in atherosclerosis process. On the other hand, controlling both Th1 and Th2 responses and regulation of the VCAM-1 are the theories introduced for regulatory role of IL-17 in atherosclerosis. 
Regardless of the exact role of IL-17 in the arthrosclerosis process, our study did not find any significant differences in the serum level of IL-17 in individuals with or without ACS and therefore did not support the theory in which IL-17 has deleterious role in atherosclerosis. However, certain limitations of this study, including inadequate number of participants and possible co-morbidities of the cases must be taken into consideration.
| Acknowledgments|| |
We thank Mr. Mohsen Aghajanpour and Ms. Narges Mousavi for their cooperation in the measurement of IL-17, to Dr. Evangeline Foronda for the English editing of the manuscript, the Deputy of Research of Babol University of Medical Sciences for the financial support and to the staffs of Babol Blood Center and Cardiology Ward of Shahid Beheshti and Rouhani Hospitals.
| References|| |
|1.||Roger VL, Jacobsen SJ, Weston SA, Goraya TY, Killian J, Reeder GS, et al. Trends in the incidence and survival of patients with hospitalized myocardial infarction, Olmsted County, Minnesota, 1979 to 1994. Ann Intern Med 2002;136:341-8. |
|2.||Guidry UC, Evans JC, Larson MG, Wilson PW, Murabito JM, Levy D. Temporal trends in event rates after Q-wave myocardial infarction: The Framingham Heart Study. Circulation 1999;100:2054-9. |
|3.||Tiong AY, Brieger D. Inflammation and coronary artery disease. Am Heart J 2005;150:11-8. |
|4.||Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 2001;104:365-72. |
|5.||Hansson GK, Libby P. The immune response in atherosclerosis: A double-edged sword. Nat Rev Immunol 2006;6:508-19. |
|6.||Hansson GK, Libby P, Schönbeck U, Yan ZQ. Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ Res 2002;91:281-91. |
|7.||Tedgui A, Mallat Z. Cytokines in atherosclerosis: Pathogenic and regulatory pathways. Physiol Rev 2006;86:515-81. |
|8.||Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol 2009;27:485-517. |
|9.||Miossec P, Korn T, Kuchroo VK. Interleukin-17 and type 17 helper T cells. N Engl J Med 2009;361:888-98. |
|10.||Ghoreschi K, Laurence A, Yang XP, Hirahara K, O′Shea JJ. T helper 17 cell heterogeneity and pathogenicity in autoimmune disease. Trends Immunol 2011;32:395-401. |
|11.||McKenzie BS, Kastelein RA, Cua DJ. Understanding the IL-23-IL-17 immune pathway. Trends Immunol 2006;27:17-23. |
|12.||Pappu R, Ramirez-Carrozzi V, Ota N, Ouyang W, Hu Y. The IL-17 family cytokines in immunity and disease. J Clin Immunol 2010;30:185-95. |
|13.||Iwakura Y, Ishigame H, Saijo S, Nakae S. Functional specialization of interleukin-17 family members. Immunity 2011;34:149-62. |
|14.||Moseley TA, Haudenschild DR, Rose L, Reddi AH. Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev 2003;14:155-74. |
|15.||Hata K, Andoh A, Shimada M, Fujino S, Bamba S, Araki Y, et al. IL-17 stimulates inflammatory responses via NF-kappaB and MAP kinase pathways in human colonic myofibroblasts. Am J Physiol Gastrointest Liver Physiol 2002;282:G1035-44. |
|16.||Taleb S, Romain M, Ramkhelawon B, Uyttenhove C, Pasterkamp G, Herbin O, et al. Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosis. J Exp Med 2009;206:2067-77. |
|17.||Jafarzadeh A, Esmaeeli-Nadimi A, Nough H, Nemati M, Rezayati MT. Serum levels of interleukin (IL)-13, IL-17 and IL-18 in patients with ischemic heart disease. Anadolu Kardiyol Derg 2009;9:75-83. |
|18.||Damås JK, Waehre T, Yndestad A, Otterdal K, Hognestad A, Solum NO, et al. Interleukin-7-mediated inflammation in unstable angina: Possible role of chemokines and platelets. Circulation 2003;107:2670-6. |
|19.||Eid RE, Rao DA, Zhou J, Lo SF, Ranjbaran H, Gallo A, et al. Interleukin-17 and interferon-gamma are produced concomitantly by human coronary artery-infiltrating T cells and act synergistically on vascular smooth muscle cells. Circulation 2009;119:1424-32. |
|20.||Simon T, Taleb S, Danchin N, Laurans L, Rousseau B, Cattan S, et al. Circulating levels of interleukin-17 and cardiovascular outcomes in patients with acute myocardial infarction. Eur Heart J 2013;34:570-7. |
|21.||Liuzzo G, Trotta F, Pedicino D. Interleukin-17 in atherosclerosis and cardiovascular disease: The good, the bad, and the unknown. Eur Heart J 2013;34:556-9. |
[Table 1], [Table 2]