Iranian Journal of Allergy, Asthma and Immunology 2017. 16(1):14-20.

Effects of Submaximal Aerobic Exercise on Regulatory T Cell Markers of Male Patients Suffering from Ischemic Heart Disease
Fariba Raygan, Mansour Sayyah, Seyed Mohammad Reza Janesar Qamsari, Hassan Nikoueinejad, Mojtaba Sehat


There are confirmed beneficiary effects of exercise on atherosclerotic inflammation of ischemia-associated heart diseases. The purpose of this study was to evaluate the effect of aerobic exercise on T-regulatory cell markers of IL-35 as well as FoxP3 and T-helper2 marker of IL-33 in patients with ischemic heart disease (IHD). This research was performed on 44 asymptomatic male patients with ischemic heart disease. The participants were randomly assigned into two groups of submaximal aerobic exercise and control group. Blood samples were collected before and after the termination of the exercise protocol. Serum levels of IL-35 and IL-33 as well as the amount of FoxP3 gene expression in peripheral blood mononuclear cells were measured by Elisa and Real time PCR, respectively. Serum levels of IL-35 (p=0.001) as well as the amount of FoxP3 gene expression increased significantly (p=0.012)  in exercise group even after controlling the likely confounding effects of age, length of ischemia, duration of the disease, and the amount of such factors before exercise (p≤0.042). It seems that exercise may yield a better control of atherosclerotic inflammation in patients with ischemic heart disease through the induction of regulatory T cells. 


Interleukin-35; Interleukin-33; Regulatory T cells; Sub maximal aerobic exercise

Full Text:



1. Paffenbarger RS Jr, Hyde RT, Wing AL, Lee IM, Jung DL, Kampert JB. The association of changes in physical activity level and other lifestyle characteristics with mortality among men. N Engl J Med 1993, 328(8):538–45.

2. Eaton SB, Eaton SB. Physical Inactivity, Obesity, and Type 2 Diabetes: An Evolutionary Perspective. Res QExerc Sport 2017; 27:1-8. doi:10.1080/02701367.2016.1268519. PMID: 28129048.

3. Mendis S, Thygesen K, Kuulasmaa K, Giampaoli S, Mähönen M, Ngu Blackett K, et al. World Health Organization definition of myocardial infarction: 2008–09 revision. Int J Epidemiol 2011; 40(1):139-46.

4. Elena Galkina and Klaus Ley, Immune and Inflammatory Mechanisms of Atherosclerosis, Annu Rev Immunol. Annu Rev Immunol 2009; 27:165–97. doi:10.1146/annurev.immunol.021908.132620.

5. Scott M. Grundy. Rationale for Cholesterollowering Strategies Current Problems in Cardiology 1995;20(5):286-357.

6. Peter W. F. Wilson, Ralph B. D’Agostino, Daniel Levy, Albert M. Belanger, Halit. Prediction of Coronary Heart Disease Using Risk Factor Categories, Circulation 1998;97:1837-47.

7. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002; 347(20):1557-65.

8. Ross R. Atherosclerosis –an inflammatory disease. N Engl J Med 1999; 340(2):115-26.

9. Zwaka TP, Hombach V, Torzawski J. C-reactive protein- mediated low density lipoprotein uptake by macrophages implications for atherosclerosis. Circulation 2001;103(9):1194–7.

10. Blaschke F, Bruemmer D, Yin F, Takata Y, Wang W, Fishbein MC, et al. C-reactive protein induces apoptosis in human coronary vascular smooth muscle cells. Circulation 2004; 110(5):579–87.

11. Grau AJ, Boddy AW, Dukovic DA, Buggle F, Lichy C, Brandt T, et al. Leukocyte count as an independent predictor of recurrent ischemic events. Stroke 2004;35(5):1147–52.

12. Lavie CJ, Thomas RJ, Squires RW, et al: Exercise training and cardiac rehabilitation in primary and secondary prevention of coronary heart diseases. Mayo Clin Proc 2009; 84(4):373-83.

13. Hartham SM, Lavie CJ, Milani RV, et al. Benefits of exercise training in secondary prevention of coronary and peripheral arterial disease. Vasc Dis Prev 2008; 5:156-68.

14. Lavie CJ, Milani RV: Cardiac rehabilitation update 2008- biological, psychological, and clinical benefits. US Cardiol 2008; 5:72-5.

15. Wenger NK. Status of cardiac rehabilitation. J Am Coll Cardiol 2008; 51(17):1619-31.

16. Thomas RJ. Cardiac rehabilitation/secondary prevention programs Craft for the rapids: why have we missed the. Raygan, et al.boat? Circulation 2007; 116(15):1644-6.

17. Milani RV, Lavie CJ. Prevalence and profile of metabolic syndrome in patients following acute coronary events and effects of therapeutic lifestyle change with cardiac rehabilitation. Am J Cardiol 2003; 92(1):50-4.

18. Lavie CJ, Milani RV, Artham SM, Patel DA, Ventura HO. The obesity paradox, weight loss, and coronary disease. Am J Med 2009; 122(12):1106-14.

19. Lavie CJ, Milani RV. Effects of cardiac rehabilitation, exercise training, and weight reduction on exercise capacity, coronary riskfactors, behavioral characteristics, and quality of life in obesecoronary patients. Am J Cardiol 1997; 79(4):397-401.

20. Lavie CJ, Morshedi-Meibodi A, Milani RV. Impact of cardiac rehabilitation on coronary risk factors, inflammation, and themetabolic syndrome in obese coronary patients. J Cardiometab Syndr 2008; 3(3):136-40.

21. Cardenas GA, Lavie CJ, Cardenas V, Milani RV, McCullough PA. The importance of recognizing and treating low levels of high-density lipoprotein cholesterol: a new era in atherosclerosis management. Rev Cardiovasc Med 2008; 9(4):239-58.

22. Fulya Ilhan and Sevgi Tas Kalkanli, Atherosclerosis and the role of immune cells, World J Clin Cases. 2015 Apr

16; 3(4):345–52. doi: 10.12998/wjcc.v3.i4.345 PMCID:PMC4391004

23. Rozanski A, Blumenthal JA, Davidson KW, Saab PG, Kubzansky L. The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology. J Am Coll Cardiol 2005; 45(5):637-51.

24. Lavie CJ, Milani RV. Effects of cardiac rehabilitation and exercise training programs on coronary patients with high levels of hostility. Mayo ClinProc 1999; 74(10):959-66.

25. Liew FY, Pitman NI, McInnes IB. Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol 2010; 10(2):103-10.

26. Czyzewska-Buczyńska A, Zuk N, Romanowska- Micherda K, Witkiewicz W. Biological role of Interleukin

33 and its importance in pathophysiology of cardiovascular system]. , Postepy Hig Med Dosw 2014;68:834-41.

27. Milovanovic M, Volarevic V, Radosavljevic G, Jovanovic I, Pejnovic N, Arsenijevic N, et al. IL-33/ST2 axis in inflammation and immunopathology. Immunol Res 2012; 52(1-2):89-99.

28. Milani RV, Lavie CJ, Mehra MR, Ventura HO. Impact of exercise training and depression on survival in heart failure due to coronary heart disease. Am J Cardiol 2011;107(1):64-8.

29. Dwyer, G.B. and Davis, S.H., America College of Sport Medicine, health-related physical fitness assessment manual, second edition, 2008;112-6.

30. Heeschen C, Dimmeler S, Hamm CW, Fichtlscherer S, Boersma E, Simoons ML, et al. Serum level of the antiinflammatory cytokine interleukin-10 is an important prognostic determinant in patients with acute coronary syndromes.Circulation 2003; 107(16):2109–14.

31. Li X, Mai J, Virtue A, Yin Y, Gong R, Sha X, et al. IL-35 is a novel responsive anti-inflammatory cytokine - a new system of categorizing anti-inflammatory cytokines. PLoS ONE 2012; 7(3):e33628.

32. Milani RV, Lavie CJ. Impact of cardiac rehabilitation on depression and its associated mortality. Am J Med 2007;120(9):799-806.

33. Ranković G, Milicić B, Savić T, Dindić B, Mancev Z, Pesić G. Effects of physical exercise on inflammatory parameters and risk for repeated acute coronary syndrome in patients with ischemic heart. Vojnosanit Pregl 2009;66(1):44-8.

34. Pedersen BK. The anti-infl amatory effect of exercise: its role in diabetes and cardiovascular disease control. Essays Biochem 2006; 42:105-17.

35. Khazaei HA, Jalili A, Andarzy S. The effect of one session intense anaerobic exercise (Bruce test) on serum level of IL-6 and IL-33 in volleyballs athletes. Annals of Biological Research, 2014, 5(2):99-104.

36. Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, et al. Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature 2010; 463(7280):540-4.


  • There are currently no refbacks.

Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.