Inflammation has been found to play a role in the etiology of cardiovascular disease as well as provoke endothelial dysfunction. Inflammatory cytokines associated with endothelial function are interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). IL-6 is exercise intensity dependent and has been shown to inhibit TNF-α expression directly. The aim of this study was to investigate the interaction of IL-6 and TNF-α on endothelial function in response to acute exercise in overweight men exhibiting different physical activity profiles.Methods and Procedures: Using a randomized mixed factorial design, 16 overweight men (8 active, maximal exercise capacity (VO2peak) = 34.2 ± 1.7, BMI = 27.4 ± 0.7 and 8 inactive, VO2peak = 30.9 ± 1.2, BMI = 29.3 ± 1.0) performed three different intensity acute exercise treatments. Brachial artery flow-mediated dilation (FMD) and subsequent blood samples were taken pre-exercise and 1 h following the cessation of exercise.Results: Independent of exercise intensity, the active group displayed a 24% increase (P = 0.034) in FMD following acute exercise compared to a 32% decrease (P = 0.010) in the inactive group. Elevated (P <0.001) concentrations of IL-6 following moderate (50% VO2) and high (75% VO2) intensity acute exercise were observed in both groups; however, concentrations of TNF-α were unchanged in response to acute exercise (P = 0.584).Discussion: The FMD response to acute exercise is enhanced in active men who are overweight, whereas inactive men who are overweight exhibit an attenuated response. The interaction of IL-6 and TNF-α did not provide insight into the physiological mechanisms associated with the disparity of FMD observed between groups.
Bibliographical noteReference text: 1. Eckel RH, Krauss RM. American Heart Association call to action: obesity as a major risk factor for coronary heart disease. Circulation 1998;97:2099–2100.
2. Lusis AJ. Atherosclerosis. Nature 2000;407:233–241.
3. Ross R. The pathogenesis of atherosclerosis-an update. N Engl J Med 1986;314:488–500.
4. Munro JM, Cotran RS. The pathogenesis of atherosclerosis: atherogenesis and inflammation. Lab Invest 1988;58:249–261.
5. Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Elevated C-reactive protein levels in overweight and obese adults. JAMA 1999;282:2131–2135.
6. Blair SN, Kohl HW 3rd, Paffenbarger RS Jr et al. Physical fitness and all cause mortality. A prospective study of healthy men and women. JAMA
1989;262:2395–2401. 7. Lee CD, Blair SN, Jackson AS. Cardiorespiratory fitness, body composition, and all-cause and cardiovascular disease mortality in men. Am J Clin Nutr
8. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med 1999;340:115–126.
9. Stenvinkel P. Endothelial dysfunction and inflammation-is there a link? Nephrol Dial Transplant 2001;16:1968–1971.
10. Koenig W, Sund M, Frohlich M et al. C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation 1999;99:237–242.
11. Ridker PM, Rifai N, Pfeffer M et al. Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation 2000;101:2149–2153.
12. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000;101:1767–1772.
13. Pedersen BK, Steensberg A, Schjerling P. Muscle-derived interleukin-6: possible biological effects. J Physiol 2001;536:329–337.
14. Febbraio MA, Pedersen BK. Contraction induced myokine production and release: Is skeletal muscle an endocrine organ? Exerc Sport Sci Rev 2005;33:114–119.
15. Steensberg A, Keller C, Starkie RL et al. IL-6 and TNF-a expression in, and release from, contracting human skeletal muscle. Am J Physiol Endocrinol Metab 2002;283:E1272–E1278.
16. Drenth JP, Van Uum SH, Van Deuren M et al. Endurance run increases circulating IL-6 and IL-1ra but downregulates ex vivo TNF-alpha and IL-1 beta production. J Appl Physiol 1995;79:1497–1503.
17. Benjamin E, Larson M, Keys MJ et al. Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham Feart Study. Circulation 2004;109:613–619.
18. Harvey PJ, Morris BL, Kubo T et al. Hemodynamic after-effects of acute dynamic exercise in sedentary normotensive postmenopausal women. Hypertension 2005;23:285–292.
19. Higashi Y, Yoshizumi M. Exercise and endothelial function: role of endothelium-derived nitric oxide and oxidative stress in healthy subjects and hypertensive patients. Pharmacol Ther 2004;102:87–96.
20. U.S. Department of Health and Human Services. Physical Activity and Health: A Report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention National Center for Injury Prevention and Control Chronic Disease Prevention and
Health Promotion (Eds.) Atlanta, GA, 1996.
21. Mitchell GF, Parise H, Vita JA et al. Local shear stress and brachial artery flow-mediated dilation. Hypertension 2004;44:134–139.
22. Ainsworth BE, Jacobs DR Jr, Leon AS. Validity and reliability of self-reported physical activity status: the Lipid Research Clinics questionnaire. Med sci sports exerc 1993;25:92–98.
23. Hein H, Suadicani P, Gyntelberg F. Physical fitness or physical activity as a predictor of ishaemic heart disease? A 17-year follow-up in the Copenhagen male study. J Intern Med 1992;232:467–469.
24. Blair SN, Kohl HW, Paffenbarger RS, Clark DG, Cooper KH. Physical fitness and all cause mortality. JAMA 1999;262:239525. Van Guilder G, Hoetzer G, Greiner J, Stauffer B, DeSouza C. Influence of metabolic syndrome on biomarkers of oxidative stress and inflammation in obese adults. Obesity (Silver Spring) 2006;14:2127–2131.
26. Yamashita N, Kamiya K, Yamada K. Experience with a programmable valve shunt system. J Neurosurg 1999;91:26–31.
27. Gokce N, Vita JA, Bader DS et al. Effect of exercise on upper and lower extremity endothelial function in patients with coronary artery disease. Am J Cardiol 2002;90:124–127.
28. Kasikcioglu E, Oflaz H, Kasikcioglu HA et al. Endothelial flow mediated dilation and exercise capacity in highly trained endurance athletes. Tohoku J Exp Med 2005;205:45–51.
29. Higashi Y, Oshima T, Ozono R. Aging and severity of hypertension attenuate endothelium-dependent renal vascular relaxation in humans. Hypertension 1997;30:252–258.
30. Wang J, Wolin MS, Hintze TH. Chronic exercise enhances endothelium-mediated dilation fo epicardial coronary artery in conscious dogs. Circ Res 1993;73:829–838.
31. Forjaz CL, Cardoso CG, Rezk CC, Santaella DF, Tinucci T. Postexercise hypotension and hemodynamics: the role of exercise intensity. J Sports Med Phys Fitness 2004;44:54–62.
32. Kemi OJ, Haram PM, Loennechen JP et al. Moderate vs high exercise intensity: differential effects on aerobic fitness, cardiomyocyte contractility, and endothelial function. Cardiovasc Res 2005;67:161–172.
33. Goto C, Higashi Y, Kimura M et al. Effect of different intensities of exercise on endothelium-dependent vasodilation in humans: role of endothelium-dependent nitric oxide and oxidative stress. Circulation 2003;108:530–535.
34. Thompson PD, Crouse SF, Goodpaster B et al. The acute versus chronic response to exercise. Med Sci Sports Exerc 2001;33(Suppl 6):S438–S445.
35. DeSouza CA, Shapiro LF, Clevenger CM et al. Regular aerobic exercise prevents and restores age-related declines in endothelium dependent vasodilation in healthy men. Circulation 2000;102:1351–57.
36. Wessel TR, Arant CB, Olson MB et al. Relationship of physical fitness vs body mass index with coronary artery disease and cardiovascular events in women. JAMA 2004;292:1179–1187.
37. Adams V, Linke A, Kränkel N et al. Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease. Circulation 2005;111:555–562.
38. Ji LL. Antioxidants and oxidative stress in exercise. Proc Soc Exp Biol Med 1999;222:283–292.
39. Hardin DS, Azzarelli B, Edwards J et al. Mechanisms of enhanced insulin sensitivity in endurance trained athletes: effects of blood flow and differential expression on GLUT-4 in skeletal muscle. J Clin Endocrinol Metab 1995;80:2437–3446.
40. Vincent HK, Morgan JW, Vincent KR. Obesity exacerbates oxidative stress levels after acute exercise. Med Sci Sports Exerc 2004;36:772–79.
41. Matsuoka H. Endothelial dysfunction associated with oxidative stress in human. Diab Res Clin Pract 2001;54:S65–S72.
42. Goodpaster BH, Katsiaras A, Kelley DE. Enhanced fat oxidation through physical activity is associated with improvements in insulin sensitivity in obesity. Diabetes 2003;52:2191–2197.