Physical inactivity increases the risk of type 2 diabetes, cardiovascular diseases, chronic obstructive pulmonary disease, colon cancer, breast cancer, dementia and depression.
Physical inactivity leads to the accumulation of visceral fat and consequently the activation of a network of inflammatory pathways. Chronic inflammation promotes the development of insulin resistance, atherosclerosis, neurodegeneration and tumour growth, and subsequently the development of a number of diseases associated with physical inactivity.
The protective effect of exercise against chronic inflammation-associated diseases may, to some extent, be ascribed to an anti-inflammatory effect of regular exercise. The anti-inflammatory effect of regular exercise may be mediated by a reduction in visceral fat mass (with a subsequent decreased release of adipokines from adipose tissue) and/or by the induction of an anti-inflammatory environment with each bout of exercise.
Possible mechanisms by which exercise exerts its anti-inflammatory effect include: release of interleukin-6 (IL-6) into the circulation from contracting muscle fibres and subsequent increases in circulating levels of IL-10 and IL-1 receptor antagonist; increased circulating numbers of IL-10-secreting regulatory T cells; downregulation of Toll-like receptor expression on monocytes and inhibition of downstream responses (such as pro-inflammatory cytokine production, antigen presentation and co-stimulatory molecule expression); reduction in the circulating numbers of pro-inflammatory monocytes; and inhibition of monocyte and/or macrophage infiltration into adipose tissue.
Although regular moderate exercise is associated with a reduced incidence of infection compared with a completely sedentary state, the long hours of hard training undertaken by elite athletes appear to make these individuals more susceptible to infections. This is also probably attributable to the anti-inflammatory effects of exercise inducing a degree of immunosuppression.
Important remaining questions on the anti-inflammatory effects of exercise include: what is the independent contribution of an exercise-induced reduction in visceral fat versus other exercise-induced anti-inflammatory mechanisms? What is the relative importance of the different anti-inflammatory mechanisms? What modes, intensities and durations of exercise are required to optimize the anti-inflammatory effects of exercise?
Regular exercise reduces the risk of chronic metabolic and cardiorespiratory diseases, in part because exercise exerts anti-inflammatory effects. However, these effects are also likely to be responsible for the suppressed immunity that makes elite athletes more susceptible to infections. The anti-inflammatory effects of regular exercise may be mediated via both a reduction in visceral fat mass (with a subsequent decreased release of adipokines) and the induction of an anti-inflammatory environment with each bout of exercise. In this Review, we focus on the known mechanisms by which exercise — both acute and chronic — exerts its anti-inflammatory effects, and we discuss the implications of these effects for the prevention and treatment of disease.
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- Type 2 diabetes mellitus
A disorder of glucose homeostasis that is characterized by inappropriately increased blood glucose levels and resistance of tissues to the action of insulin. Recent studies indicate that inflammation in adipose tissue, liver and muscle contributes to the insulin-resistant state that is characteristic of type 2 diabetes mellitus, and that the anti-diabetic actions of peroxisome proliferator-activated receptor-γ agonists result, in part, from their anti-inflammatory effects in these tissues.
This term has been recently introduced to describe the multilevel interactions between the metabolic and immune systems.
Factors, including cytokines, that are secreted from adipose tissue. Some adipokines promote inflammatory responses and metabolic dysfunction, whereas others have anti-inflammatory functions and beneficial effects on metabolic disorders.
- Insulin resistance
A condition characterized by the inability of cells in the muscle, liver and adipose tissue to respond appropriately to endogenous insulin, resulting in increased blood glucose levels.
The storage form of fat found in adipose tissue.
- Low-density lipoprotein
(LDL). A protein–lipid complex in the blood plasma that facilitates the transport of triglycerides, cholesterol and phospholipids. High blood levels of LDL are associated with an increased risk of coronary heart disease.
- High-density lipoprotein
(HDL). A protein–lipid complex in the blood plasma that facilitates the transport of triglycerides, cholesterol and phospholipids. High blood levels of HDL are associated with a decreased risk of coronary heart disease.
- Regulatory T cells
(TReg cells). A specialized subpopulation of T cells that acts to suppress activation of the immune system and thereby maintains immune system homeostasis and tolerance to self antigens. These cells are involved in shutting down immune responses after they have successfully tackled invading microorganisms, and also in regulating immune responses that may potentially attack one's own tissues (autoimmunity).
A regulatory hormone that is produced by adipocytes. When released into the circulation, it influences the hypothalamus to control appetite, and its production correlates with the amount of adipose tissue.
A cytokine released from adipocytes that has anti-inflammatory effects and acts as an insulin sensitizer.
A steroid hormone secreted from the adrenal cortex in response to stress that has anti-inflammatory as well as catabolic effects.
A catecholamine secreted from the adrenal medulla in response to stress that has effects on the cardiovascular system (for example, increased heart rate and peripheral vasoconstriction) and on metabolism (for example, increased glycogen breakdown and lipolysis). It also has some immunosuppressive effects (for example, decreased pro-inflammatory cytokine production by monocytes and lymphocytes).
- Hypothalamic–pituitary–adrenal axis
A major component of the stress system that consists of the paraventricular nucleus (PVN) of the hypothalamus, the anterior pituitary gland and the adrenal cortices. Corticotropin-releasing hormone and vasopressin secreted by PVN neurons into the hypophyseal portal system stimulate pituitary cells to produce and secrete adrenocorticotropic hormone (ACTH) into the general circulation. ACTH then stimulates cortisol secretion by the adrenal glands.
- Sympathetic nervous system
A part of the nervous system that serves to accelerate the heart rate, constrict blood vessels, raise blood pressure and mobilize metabolic fuels. It is responsible for the 'fight-or-flight response' to stress and physical activity (that is, the non-volitional preparation of the organism for emergency situations).
- Adrenocorticotropic hormone
A peptide hormone secreted from the anterior pituitary gland that stimulates the release of cortisol from the adrenal glands.
A catecholamine secreted from sympathetic nerve endings that has effects on the cardiovascular system (for example, increased heart rate and peripheral vasoconstriction) and on metabolism (for example, increased glycogen breakdown and lipolysis). It also has some immunosuppressive effects (for example, decreased pro-inflammatory cytokine production by monocytes and lymphocytes).
- M1-type macrophages
Macrophages that are activated in the presence of TH1-type cytokines, such as interferon-γ, and produce, among other molecules, inducible nitric oxide synthase and nitric oxide.
- M2-type macrophages
Macrophages that are activated in the presence of TH2-type cytokines, such as interleukin-4 (IL-4) or IL-13, and express arginase 1, the mannose receptor CD206 and the IL-4 receptor α-chain.
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Gleeson, M., Bishop, N., Stensel, D. et al. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol 11, 607–615 (2011). https://doi.org/10.1038/nri3041
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