The anti-inflammatory effect of exercise

The anti-inflammatory effect of exercise | Journal of Applied Physiology– 1 April 2005

This long and detailed article explains the biochemistry of exercise and how it can reduce chronic low-grade inflammation.

Regular exercise offers protection against all-cause mortality, primarily by protection against cardiovascular disease and Type 2 diabetes mellitus.

The latter disorders have been associated with chronic low-grade systemic inflammation reflected by a two- to threefold elevated level of several cytokines.

Adipose tissue contributes to the production of TNF-α, which is reflected by elevated levels of soluble TNF-α receptors, IL-6, IL-1 receptor antagonist, and C-reactive protein.  

We suggest that TNF-α rather than IL-6 is the driver behind insulin resistance and dyslipidemia and that IL-6 is a marker of the metabolic syndrome, rather than a cause.

During exercise, IL-6 is produced by muscle fibers via a TNF-independent pathway. IL-6 stimulates the appearance in the circulation of other anti-inflammatory cytokines such as IL-1ra and IL-10 and inhibits the production of the proinflammatory cytokine TNF-α.

In addition, IL-6 enhances lipid turnover, stimulating lipolysis as well as fat oxidation.

We suggest that regular exercise induces suppression of TNF-α and thereby offers protection against TNF-α-induced insulin resistance.

Recently, IL-6 was introduced as the first myokine, defined as a cytokine that is produced and released by contracting skeletal muscle fibers, exerting its effects in other organs of the body.

Here we suggest that myokines may be involved in mediating the health-beneficial effects of exercise and that these in particular are involved in the protection against chronic diseases associated with low-grade inflammation such as diabetes and cardiovascular diseases.

Given that chronic low-grade systemic inflammation may be involved in atherosclerosis and diabetes pathogenesis (24, 69) and given the recent finding that physical activity induces an increase

in the systemic levels of a number of cytokines with anti-inflammatory properties, we discuss the possibility that physical exercise exerts anti-inflammation and thereby protects against chronic medical disorders associated with low-grade systemic inflammation.  


Cross-sectional studies demonstrate an association between physical inactivity and low-grade systemic inflammation in healthy subjects (1, 31, 45, 62, 73, 124, 140, 156) in elderly people (16), as well as in patients with intermittent claudication (143).

These correlational data do, however, not provide any information with regard to a possible causal relationship.

The finding in two longitudinal studies that regular training induces a reduction in CRP level (31, 73) suggests that physical activity as such may suppress systemic low-grade inflammation.

To study whether acute exercise induces a true anti-inflammatory response, our laboratory developed a model of “low-grade inflammation” in which we injected a low dose of Escherichia coli endotoxin to healthy volunteers, who had been randomized to either rest or exercise before endotoxin administration.

In resting subjects, endotoxin induced a two- to threefold increase in circulating levels of TNF-α. In contrast, when the subjects performed 3 h of ergometer cycling and received the endotoxin bolus at 2.5 h, the TNF-α response was totally blunted (127).

The finding that exercise suppresses endotoxin-induced TNF-α production was supported by a recent study demonstrating that exercise normalizes overexpression of TNF-α in TNF-R knockout mice (57).

I’ve only annotated the abstract and another small piece of this long and detailed article. The article outline is below:



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