European Heart Journal Advance Access originally published online on April 13, 2006
European Heart Journal 2006 27(11):1385; doi:10.1093/eurheartj/ehi867
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Exercise and inflammation
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Low-grade systemic inflammation is present in subjects with insulin resistance, obesity, type-2 diabetes mellitus, hypertension, hyperlipidaemia, and metabolic syndrome X.1–3 The results of the study reported by Lakka et al.4 suggest that exercise reduces the concentrations of pro-inflammatory molecule C-reactive protein. These results are in support of my earlier proposition that exercise is anti-inflammatory in nature.5
Studies revealed that exercise not only decreased the levels of pro-inflammatory cytokines IL-6, TNF-
, and C-reactive protein but also simultaneously enhanced the concentrations of anti-inflammatory cytokines IL-4, IL-10 and TGF-ß compared when with controls. IL-4, IL-10 and TGF-ß are not only anti-inflammatory in nature but also suppress the production of pro-inflammatory cytokines IL-1, IL-2, and TNF-.5 In experimental animals, exercise significantly reduced the magnitude of myocardial infarction and this cardioprotective action paralleled the increase in manganese superoxide dismutase (Mn-SOD) activity.6 The administration of antisense oligo-deoxyribonucleotide to Mn-SOD abolished this cardioprotective action implying that ability of exercise to enhance the activity of Mn-SOD is crucial to this protective action. Obviously, this increase in Mn-SOD activity is in response to exercise-induced free radical generation suggesting that under certain circumstances free radicals have highly beneficial actions, especially when they are produced in response to physiological stimulus such as exercise. Even pro-inflammatory cytokines enhance free radical generation. It is interesting to note that administration of antibodies to TNF- and IL-1 abolished the cardioprotective action of exercise and activation of Mn-SOD. These results indicate that exercise-induced increase in the production of pro-inflammatory cytokines augment the production of free radicals that, in turn, augment Mn-SOD activity, which is ultimately responsible for the cardioprotective action of exercise. This is supported by the observation that circulating levels of extracellular SOD are lower in subjects with CHD.7 Furthermore, SOD enhances the half-life of nitric oxide, a potent vasodilator, platelet anti-aggregator, and anti-atherosclerotic molecule. It is noteworthy that supplementation of anti-oxidant vitamin E counteracted the beneficial effects of exercise, suggesting that stimulation of endogenous anti-oxidants such as Mn-SOD is more critical to the beneficial actions of exercise and this benefit cannot be imitated by exogenous administration of anti-oxidants. Thus, regular exercise ensures adequate expression of endogenous anti-oxidants and anti-inflammatory cytokines and thus, brings about its cardioprotective action. In this context, the ability of exercise to suppress C-reactive protein levels is interesting and re-emphasizes the anti-inflammatory nature of exercise. A better understanding of the molecular mechanism(s) of the beneficial actions of exercise could lead to development of more precise therapeutic strategies both in the prevention and treatment of cardiovascular and other diseases.
References
- Das UN. (2001) Is obesity an inflammatory condition? Nutrition 17:953–966.[CrossRef][Web of Science][Medline]
- Das UN. (2002) Is metabolic syndrome X an inflammatory condition? Exp Biol Med 227:989–997.
[Abstract/Free Full Text] - Das UN. (2002) Obesity, metabolic syndrome X, and inflammation. Nutrition 18:430–432.[CrossRef][Web of Science][Medline]
- Lakka TA, Lakka HM, Rankinen T, Leon AS, Rao DC, Skinner JS, Wilmore JH, Bouchard C. (2005) Effect of exercise training on plasma levels of C-reactive protein in healthy subjects: the HERITAGE Family Study. Eur Heart J 26:2018–2025.
[Abstract/Free Full Text] - Das UN. (2004) Anti-inflammatory nature of exercise. Nutrition 20:323–326.[CrossRef][Medline]
- Yamashita N, Hoshida S, Otsu K, Asahi M, Kuzuya T, Hori M. (1999) Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation. J Exp Med 189:1699–1706.
[Abstract/Free Full Text] - Wang XL, Adachi T, Sim AS, Wilcken DE. (1998) Plasma extracellular superoxide dismutase levels in an Australian population with coronary artery disease. Arterioscler Thromb Vasc Biol 18:1915–1921.
[Abstract/Free Full Text]
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