Edited by Dr. Cesare Squillace, PhD
It is now widely accepted by the entire scientific community that regular physical exercise determines a physiological protective response towards many of the causes of mortality, and in contrast to inflammatory phenomena such as atherosclerosis and insulin resistance. Performing regular physical exercise allows the skeletal muscles not only to contract, but also to secrete and release an anti-inflammatory cytokine: IL-6 (interleukin 6) into the bloodstream. Scientific evidence shows that it stimulates the production and release of other circulating cytokines such as IL-1ra (inteleukin-1 receptor antagonist) and IL-10 (interleukin 10); it also inhibits the production of pro-inflammatory interleukins such as TNF-α (tumor necrosis factor-alpha). IL-6 facilitates the turnover of lipids, stimulates lipolysis as well as ß-oxidation.
Numerous researches highlight how regular exercise induces TNF-α suppression by offering protection against insulin resistance generated by the cytokine itself. Recently, IL-6 has been defined as the first “myokine” produced and released by individual skeletal muscle fibers following their contraction, exerting its effects on other organs of the body as well.
We know that skeletal muscle is the largest organ in the human body; the discovery that simple muscle contraction translates not only into a biomechanical response, but also into the production of anti-inflammatory cytokines, opens up new paradigms: skeletal muscle is an endocrine organ which, through contraction, stimulates the production and release of cytokines, which can influence metabolism and modify their production in tissues and organs (figure 1).
Fig. 1 Skeletal muscle tissue must be considered an important endocrine organ, which expresses and releases cytokines (also called myokines) into the bloodstream and potentially influence the metabolism and status inflammatory in tissues and organs (from Pedersen BK, 2006).
During sepsis conditions and in experimental models, the cytokine cascade includes TNF-α, IL-1β, IL-6, IL-ra, sTNF-R and IL-10. The first two cytokines appear to be TNF-α and IL-1ß, locally produced. These cytokines are classically recognized as pro-inflammatory. These same stimulate the production of IL-6 which has been classified with both pro and anti-inflammatory action. The cytokines produced during exercise differ from those present following infections. The fact that the classic pro-inflammatory cytokines, TNF-α and IL-1ß, in general do not increase with exercise indicates that the cytokine cascade induced by "exercise differs from that induced by a common infection.
The first cytokine released into the bloodstream during exercise is IL-6. The circulating levels of the same increase exponentially (100 times more) in response to exercise, and decrease in the post-exercise period (Figure 2).
Fig. 2 During a chronic inflammatory state caused by a "systemic type infection (left), the cytokine cascade within the first hours is represented by TNF-α, IL-6, IL-1ra, sTNF-R and IL-10 The cytokines in response to exercise (right) do not include TNF-α but show a marked increase in IL-6, which is followed by IL-ra, sTNF-R and IL-10. There is no evidence of increases in the levels of C reactive protein (CRP) (from Pedersen BK, 2006).
In summary, we can say that regular physical exercise generates an anti-inflammatory response that is expressed through the production of an important cytokine such as IL-6. It acts on different tissues and at the same time stimulates the production of IL-ra and IL. -10, by inhibiting the pro-inflammatory cytokine TNF-α. Then the skeletal muscle, through simple muscle contraction, produces and releases "myokines" that mediate the beneficial effects of physical exercise and play a fundamental role, protecting and counteracting a state of chronic inflammation such as that found in cardiovascular disease and type 2 diabetes.
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