European Heart Journal Advance Access originally published online on April 13, 2006
European Heart Journal 2006 27(11):1385-1386; doi:10.1093/eurheartj/ehi868
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Exercise and inflammation: reply
Institute of Biomedicine
Unit of Physiology
University of Kuopio
POB 1627
Kuopio 70210
Finland
Tel: +358 40 5776914
Fax: +358 17 163112
E-mail address: timo.lakka{at}uku.fi
Pennington Biomedical Research Center
Louisiana State University
Baton Rouge, LA
USA
Kuopio Research Institute of Exercise Medicine
Kuopio
Finland
Department of Public Health and Clinical Nutrition
University of Kuopio
Kuopio
Finland
Pennington Biomedical Research Center
Louisiana State University
Baton Rouge, LA
USA
Pennington Biomedical Research Center
Louisiana State University
Baton Rouge, LA
USA
Pennington Biomedical Research Center
Louisiana State University
Baton Rouge, LA
USA
Our recent report from the HERITAGE Family Study showed that moderate to high-intensity exercise training reduced plasma levels of C-reactive protein, an important pro-inflammatory biomarker, in sedentary healthy adults with initial C-reactive protein levels >3.0 mg/L.1 This finding is potentially important from both a public health and a clinical point of view, because individuals with C-reactive protein >3.0 mg/L represent about one-fourth of all adults and are thought to have a markedly increased risk of cardiovascular disease and type-2 diabetes. A number of studies with different designs support the view that regular physical activity suppresses the inflammatory process,2,3 an observation that could partly explain the effectiveness of regular exercise in the prevention and treatment of cardiovascular disease and type-2 diabetes.
Dr Das discussed some of the evidence that exercise reduces the levels of pro-inflammatory cytokines but increases the levels of anti-inflammatory cytokines, which in turn suppress the production of pro-inflammatory cytokines. He suggested that the exercise-induced increase in the production of pro-inflammatory cytokines augments the production of free radicals, which increases the activity of the endogenous antioxidant, manganese superoxide dismutase, ultimately responsible for the cardioprotective effect of exercise. He concluded that regular exercise ensures adequate expression of anti-inflammatory cytokines and endogenous antioxidants for the prevention of coronary heart disease.
Indeed, there is evidence for the inflammation-suppressing effects of exercise. A recent review concluded that a single bout of strenuous exercise produces a short-term, transient increase in plasma levels of C-reactive protein. The C-reactive protein increase is due to an exercise-induced acute phase response, mediated by the cytokine system and mainly IL-6.2 In contrast, exercise training may blunt the acute pro-inflammatory response, and even suppress the inflammatory process, thereby contributing to the beneficial effects of habitual physical activity.2 There also appears to be an acute homeostatic anti-inflammatory response after a bout of strenuous exercise that counteracts the pro-inflammatory response.2
A Danish research group has suggested that the inflammation-suppressing effect of exercise training is explained by the anti-inflammatory response elicited by a bout of exercise, which is partly mediated by an increase in IL-6 in skeletal muscle.3 They have shown that physiological increases in plasma levels of IL-6, produced by the contraction of skeletal muscles during exercise, stimulate the production of anti-inflammatory cytokines IL-1ra and IL-10 but inhibit the production of a pro-inflammatory cytokine TNF-
. Thus, the inflammation-suppressing effect of exercise training may protect against TNF--induced insulin resistance, one of the important pathophysiological mechanisms of type-2 diabetes.
More research is needed to better understand the molecular mechanisms by which physical activity suppresses inflammation. Randomized controlled trials are warranted to investigate the dose of regular physical activity needed for an inflammation-suppressing effect, whether moderate intensity physical activity, as currently recommended, is sufficient for the effect, and whether there are dose and intensity thresholds above which no further benefits are gained or even harmful effects occur.
References
- Lakka TA, Lakka HM, Rankinen T, Leon AS, Rao DC, Skinner JS, Wilmore JH, Bouchard C. (2005) Effect of exercise training on serum levels of C-reactive protein in healthy individuals: the HERITAGE Family Study. Eur Heart J 26:2018–2025.
[Abstract/Free Full Text] - Kasapis C and Thompson PD. (2005) The effects of physical activity on serum C-reactive protein and inflammatory markers. A systematic review. J Am Coll Cardiol 45:1563–1569.
[Abstract/Free Full Text] - Petersen AMW and Pedersen BK. (2005) The anti-inflammatory effect of exercise. J Appl Physiol 98:1154–1162.
[Abstract/Free Full Text]
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