Chapter Fourteen - Exercise and the Regulation of Inflammatory Responses

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Abstract

Exercise initiates a cascade of inflammatory events, which ultimately lead to long-term effects on human health. During and after acute exercise in skeletal muscle, interactions between immune cells, cytokines, and other intracellular components, create an inflammatory milieu responsible for the recovery and adaption from an exercise bout. In the systemic circulation, cytokines released from muscle (myokines) mediate metabolic and inflammatory processes. Moderate exercise training results in improvements in systemic inflammation, evident by reductions in acute phase proteins. The anti-inflammatory effects of regular exercise include actions dependent and independent of changes in adipose tissue mass. Future research should encompass approaches, which attempt to integrate other, less-recognized physiological processes with acute and long-term inflammatory changes. This will include investigation into metabolic, endocrine, and immune components of various tissues and organs.

Section snippets

A Brief History of Inflammation and Its Underlying Relationship to Exercise

In the first century medical encyclopedia, De Medicina, the Roman physician Conrelius Celsus first introduced four cardinals signs of inflammation, “Rubor et tumor cum colore et dolore”; or “redness and swelling with heat and pain.” Nearly two millennia later, in the mid-1800s, Rudolf Virchow introduced the fifth cardinal sign of inflammation, “function laesa”; or “loss of function,” which described the inadequate functionality of cells when exposed to a stressful stimuli.1 Virchow proposed

Exercise and Acute Inflammation in Skeletal Muscle

Muscular contraction is required for locomotion in mammals, thus skeletal muscle seems the most appropriate tissue to begin the investigation into the inflammatory processes regulated by exercise. This section will discuss the roles of metabolic and muscular injury by-products in inducing inflammatory events within skeletal muscle during and after acute exercise. We will also explore possible mechanisms by which inflammatory processes initiate long-term adaptation within skeletal muscles.

A

The Resolution of Inflammation Within Skeletal Muscle: A Coordinated Inflammatory Response

The promotion of ROS and DAMPs by exercise can and has been viewed as a deleterious response. However, there is growing evidence that many of the pro-oxidative and proinflammatory processes that occur after acute exercise may be vital for the long-term adaptive responses to exercise training.8 The temporal regulation of antioxidant enzymes and anti-inflammatory agents, which initiate metabolic adaptation and tissue repair within skeletal muscle, is evidence of such a phenomenon. The adaptive

Beyond the Muscle: Acute Exercise and Systemic Inflammation

Acute exercise can also induce changes in the inflammatory milieu in areas beyond the skeletal muscle. Massive changes in circulating cytokines (although interestingly not the prototypical proinflammatory cytokines TNF-α and IL-1β) after acute exercise are evidence of this. Notably, some of these cytokines are postulated to be released directly from skeletal muscle, and thus have been termed “myokines.”29 In addition to proposed metabolic effects,30 one particular myokine, IL-6, has pleiotropic

Summary of Acute Exercise and Inflammation

In summary, an acute exercise bout initiates a complex, time-dependent cascade of inflammatory events, which depends largely on the mode, intensity, duration, and familiarity of the exercise bout (Fig. 1). The inflammatory mediators which regulate this response act upon various tissues, most notably the skeletal muscle. Here, the inflammatory cascade is characterized by an initial proinflammatory response (~ 1.5–24 h after exercise) which is followed by an anti-inflammatory muscle regenerative

Exercise Training and Chronic Inflammation

Studies have demonstrated that chronic inflammation may increase the risk of disability and mortality even in people who do not have clinical disease.5 For instance, for individuals with infection, C-reactive protein (CRP) levels may be 1000-fold higher than the standard values.54 CRP is a hepatic acute phase protein that is commonly used as a biomarker of systemic inflammation and risk factor for cardiovascular disease (CVD) if levels are > 3 mg/L55 and, importantly, its levels have been

Potential Mechanisms of the Effect of Exercise Training on Anti-Inflammation

While the measurement of blood inflammatory biomarkers in people is informative, they do not shed light on tissue-specific inflammation or its causes. This is important because local tissue inflammation results in an increase in blood inflammatory biomarkers. Animal models assist in localizing inflammatory defects to particular tissues of interest and will aid in the identification of tissue-specific anti-inflammatory mechanisms associated with regular exercise. There are several potential

Summary

Exercise exerts a pleiotropic, time-dependent cascade of inflammatory events, which have numerous roles in health and disease. These include interactions between innate and adaptive immune cells, cytokines, and other intracellular components, which under appropriate conditions, provide an inflammatory milieu optimal for recovery, regeneration, and adaptation from an exercise bout. The inflammatory response to an acute exercise bout, however, does not necessarily provoke one type of

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