Отсутствие связи между уровнем интерлейкина-25 в сыворотке крови и острым коронарным синдромом: предварительное исследование

Цель    В настоящем исследовании впервые была оценена взаимосвязь между уровнем IL-25 и риском развития острого коронарного синдрома (ОКС) у иранских пациентов. 
Методы    Уровень IL-25 в сыворотке крови был измерен с помощь иммуноферментного анализа у 88 пациентов с ОКС, у 40 пациентов со стабильной стенокардией и у 50 здоровых людей из контрольной группы. 
Результаты    Не наблюдалось значительных различий концентрации IL-25 между пациентами со стабильной стенокардией (339,8 ± 167,6 нг / л), ОКС (329,6 ± 151,3 нг / л) и группой контроля (301,6 ± 134,8 нг / л) (р = 0,5). Также не было выявлено различий между пациентами с 1, 2 или 3 - сосудистым атеросклеротическим поражением в группах со стабильной стенокардией и ОКС. Линейный регрессионный анализ показал, что IL-25 не коррелировал с факторами риска ишемической болезни сердца в исследуемой когорте. Биохимические и демографические переменные существенно не различались между различными квартилями концентрации IL-25.
Заключение    Несмотря на предыдущие исследования на мышах и людях, посвященные защитной роли IL-25 при атеросклерозе, результаты нашей работы свидетельствуют о том, что IL-25 не имеет потенциального значения для развития и лечения атеросклероза у людей.

1. Tedgui A, Mallat Z. Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways. Physiological Reviews. 2006;86(2):515-81. https://doi.org/10.1152/physrev.00024.2005

2. Fatkhullina AR, Peshkova IO, Koltsova EK. The role of cytokines in the development of atherosclerosis. Biochemistry (Moscow). 2016;81(11):1358-70. https://doi.org/10.1134/S0006297916110134

3. Ait-Oufella H, Taleb S, Mallat Z, Tedgui A. Recent Advances on the Role of Cytokines in Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;31(5):969-79. https://doi.org/10.1161/ATVBAHA.110.207415

4. Mantani PT, Dunér P, Bengtsson E, Alm R, Ljungcrantz I, Söderberg I et al. IL-25 Inhibits Atherosclerosis Development in Apolipoprotein E Deficient Mice. PLOS ONE. 2015;10(1):e0117255. https://doi.org/10.1371/journal.pone.0117255

5. Iwakura Y, Ishigame H, Saijo S, Nakae S. Functional Specialization of Interleukin-17 Family Members. Immunity. 2011;34(2):149-62. https://doi.org/10.1016/j.immuni.2011.02.012

6. Cheng X, Yu X, Ding Y, Fu Q, Xie J, Tang T et al. The Th17/Treg imbalance in patients with acute coronary syndrome. Clinical Immunology. 2008;127(1):89-97. https://doi.org/10.1016/j.clim.2008.01.009

7. Xie J, Wang J, Tang T, Chen J, Gao X, Yuan J et al. The Th17/Treg functional imbalance during atherogenesis in ApoE−/− mice. Cytokine. 2010;49(2):185-93. https://doi.org/10.1016/j.cyto.2009.09.007

8. Zhang S, Yuan J, Yu M, Fan H, Guo Z-Q, Yang R et al. IL-17A Facilitates Platelet Function through the ERK2 Signaling Pathway in Patients with Acute Coronary Syndrome. PLoS ONE. 2012;7(7): e40641. https://doi.org/10.1371/journal.pone.0040641

9. Saenz SA, Siracusa MC, Perrigoue JG, Spencer SP, Urban Jr JF, Tocker JE et al. IL25 elicits a multipotent progenitor cell population that promotes TH2 cytokine responses. Nature. 2010;464(7293):1362-6. https://doi.org/10.1038/nature08901

10. Neill DR, McKenzie AN. TH9: the latest addition to the expanding repertoire of IL‐25 targets. Immunology & Cell Biology. 2010;88(5):502-4. https://doi.org/10.1038/icb.2010.43

11. Hams E, Locksley RM, McKenzie ANJ, Fallon PG. Cutting Edge: IL-25 Elicits Innate Lymphoid Type 2 and Type II NKT Cells That Regulate Obesity in Mice. The Journal of Immunology. 2013;191(11):5349-53. https://doi.org/10.4049/jimmunol.1301176

12. Yao X, Sun Y, Wang W, Sun Y. Interleukin (IL)-25: Pleiotropic roles in asthma: IL-25 and asthma. Respirology. 2016;21(4):638-47. https://doi.org/10.1111/resp.12707

13. Kleinschek MA, Owyang AM, Joyce-Shaikh B, Langrish CL, Chen Y, Gorman DM et al. IL-25 regulates Th17 function in autoimmune inflammation. The Journal of Experimental Medicine. 2007;204(1):161-70. https://doi.org/10.1084/jem.20061738

14. Liu D, Cao T, Wang N, Liu C, Ma N, Tu R et al. IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an IL-13-dependent manner. Scientific Reports. 2016;6(1):36002. https://doi.org/10.1038/srep36002

15. Su J, Chen T, Ji X-Y, Liu C, Yadav PK, Wu R et al. IL-25 Downregulates Th1/Th17 Immune Response in an IL-10-Dependent Manner in Inflammatory Bowel Disease: Inflammatory Bowel Diseases. 2013;19(4):720-8. https://doi.org/10.1097/MIB.0b013e3182802a76

16. Caruso R, Sarra M, Stolfi C, Rizzo A, Fina D, Fantini MC et al. Interleukin-25 Inhibits Interleukin-12 Production and Th1 Cell-Driven Inflammation in the Gut. Gastroenterology. 2009;136(7):2270-9. https://doi.org/10.1053/j.gastro.2009.02.049

17. Emamaullee JA, Davis J, Merani S, Toso C, Elliott JF, Thiesen A et al. Inhibition of Th17 Cells Regulates Autoimmune Diabetes in NOD Mice. Diabetes. 2009;58(6):1302-11. https://doi.org/10.2337/db08-1113

18. Mantani PT, Dunér P, Bengtsson E, Ljungcrantz I, Sundius L, To F et al. Interleukin-25 (IL-25) has a protective role in atherosclerosis development in the aortic arch in mice. Journal of Biological Chemistry. 2018;293(18):6791-801. https://doi.org/10.1074/jbc.RA117.000292

19. Gibbons RJ, Balady GJ, Timothy Bricker J, Chaitman BR, Fletcher GF, Froelicher VF et al. ACC/AHA 2002 guideline update for exercise testing: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). Journal of the American College of Cardiology. 2002;40(8):1531-40. https://doi.org/10.1016/S0735-1097(02)02164-2

20. Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. The American Journal of Cardiology. 1983;51(3):606. https://doi.org/10.1016/S0002-9149(83)80105-2

21. Fort MM, Cheung J, Yen D, Li J, Zurawski SM, Lo S et al. IL-25 Induces IL-4, IL-5, and IL-13 and Th2-Associated Pathologies In Vivo. Immunity. 2001;15(6):985-95. https://doi.org/10.1016/S1074-7613(01)00243-6

22. Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H et al. Innate production of TH2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells. Nature. 2010;463(7280):540-4. https://doi.org/10.1038/nature08636

23. Neill DR, Wong SH, Bellosi A, Flynn RJ, Daly M, Langford TKA et al. Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature. 2010;464(7293):1367-70. https://doi.org/10.1038/nature08900

24. Price AE, Liang H-E, Sullivan BM, Reinhardt RL, Eisley CJ, Erle DJ et al. Systemically dispersed innate IL-13-expressing cells in type 2 immunity. Proceedings of the National Academy of Sciences. 2010;107(25):11489-94. https://doi.org/10.1073/pnas.1003988107

25. Huber SA, Sakkinen P, David C, Newell MK, Tracy RP. T Helper-Cell Phenotype Regulates Atherosclerosis in Mice Under Conditions of Mild Hypercholesterolemia. Circulation. 2001;103(21):2610-6. https://doi.org/10.1161/01.CIR.103.21.2610

26. Butcher MJ, Gjurich BN, Phillips T, Galkina EV. The IL-17A/IL17RA Axis Plays a Proatherogenic Role via the Regulation of Aortic Myeloid Cell Recruitment. Circulation Research. 2012;110(5):675-87. https://doi.org/10.1161/CIRCRESAHA.111.261784

27. Erbel C, Chen L, Bea F, Wangler S, Celik S, Lasitschka F et al. Inhibition of IL-17A Attenuates Atherosclerotic Lesion Development in ApoE-Deficient Mice. The Journal of Immunology. 2009;183(12):8167-75. https://doi.org/10.4049/jimmunol.0901126

28. Smith E, Prasad K-MR, Butcher M, Dobrian A, Kolls JK, Ley K et al. Blockade of Interleukin-17A Results in Reduced Atherosclerosis in Apolipoprotein E-Deficient Mice. Circulation. 2010;121(15):1746-55. https://doi.org/10.1161/CIRCULATIONAHA.109.924886

29. de Boer OJ, van der Meer JJ, Teeling P, van der Loos CM, Idu MM, van Maldegem F et al. Differential expression of interleukin-17 family cytokines in intact and complicated human atherosclerotic plaques. The Journal of Pathology. 2010;220(4):499-508. https://doi.org/10.1002/path.2667

30. Xu Y, Ye J, Wang M, Liu J, Wang Z, Jiang H et al. Interleukin-25 increases in human coronary artery disease and is associated with the severity of coronary stenosis. The Anatolian Journal of Cardiology. 2020;23(3):151-9. https://doi.org/10.14744/AnatolJCardiol.2019.24265