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

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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.


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