By comparison, the concentration of anti-inflammatory IL-6 increased fold [ 36 ]. It can therefore be concluded that whilst strenuous exercise induces an increase in the pro-inflammatory cytokines, TNF-α and IL-1β, it is largely counteracted by the induction of anti-inflammatory cytokines leading to an overall anti-inflammatory response.

Evidence has shown that circulating levels of both interleukin 10 IL and IL-1Ra both rise in the period following exercise [ 10 ] and their release is likely upregulated in response to IL-6 [ 91 , 96 , 97 ]. IL and IL-1Ra play a role in immune regulation and have also been implicated in contributing to the anti-inflammatory response to exercise.

IL is considered a classic anti-inflammatory cytokine. It is proposed that IL suppresses cytokines through both direct inhibition of the action of pro-inflammatory cytokines, as well as by preventing cytokine synthesis [ 36 ].

In doing so, IL prevents the generation of pro-inflammatory cytokines [ 37 ]. IL inhibits a number of cytokines, including TNF-α and IL-1β, which is an important consideration in the context of exercise given that the levels of these cytokines are low despite elevated IL-6 [ 38 ].

In contrast to the action of IL, which influences a spectrum of cytokines, IL-1Ra mediates its effects on IL-1 alone. IL-1Ra inhibits signal transduction by competitively binding to IL-1 receptor complex [ 39 ], thus preventing IL-1 binding and mediating its pro-inflammatory effects.

IL-4 is an anti-inflammatory cytokine that may contribute to the overall anti-inflammatory environment observed in exercise. IL-4 mediates its action primarily through the inhibition of Th1 cells, reduction of plasma IL-1 β and upregulation of IL-1Ra [ 40 ]. The IL-4 response to exercise is less well characterised than the key mediators involved in exercise.

Studies have shown no change in IL-4 expression in the immediate aftermath of exercise [ 40 ]. However, it has been suggested that IL-4 may be involved in long-term muscular adaptations to exercise [ 41 ].

Through regular training, the expression of IL-4 within muscles has been found to increase over time following repeated individual exercise sessions [ 42 ].

This suggests that through regular training, muscles become more able to mediate some of their anti-inflammatory profile through the upregulation of IL IL has been studied alongside IL-4 due to the similarity in the actions of both cytokines.

Like IL-4, IL also inhibits T helper type 1 Th1 cells, reduces plasma IL-1b and upregulates IL-1Ra [ 40 ]. Alongside its anti-inflammatory role, it has been suggested that IL has a distinct role in exercise and metabolism.

Knudsen et al. report that endurance training in mice increases the local production of IL within muscles, which, through the activation of downstream pathways, leads to improved muscle fatty acid utilisation and mitochondrial biogenesis [ 43 ]. This response was not observed in mice which lacked IL The potential anti-inflammatory and metabolic roles of IL in exercise may provide an important focus for understanding the metabolic conditioning that can be observed through regular exercise.

Further studies are required to investigate the relationship between exercise and IL expression in humans. IL-8 belongs to the CXC family of chemokines and is primarily involved in neutrophil migration, as well as angiogenesis in vivo [ 44 ].

In the context of exercise, IL-8 is produced locally within the muscle during exercise, with a minimal systemic IL-8 response only observed following intense exercise with an eccentric component owing to the associated pro-inflammatory response in this setting [ 12 ]. The role of IL-8 in angiogenesis is distinct from its pro-inflammatory actions [ 45 ].

IL-8 acts via the stimulation of CXC receptors 1 and 2 CXCR1 and CXCR2. CXRC2 is expressed by microvascular endothelial cells and is responsible for IL-8 induced angiogenesis [ 46 ]. It has been shown that exercise induces CXCR2 mRNA and protein expression in the vascular endothelial cells of muscles [ 47 ].

This suggests muscle-derived IL-8 exerts its action locally, primarily to stimulate exercise-induced angiogenesis through CXCR2. IL is a cytokine which acts as both an immunoregulatory mediator and as a growth factor. IL is highly expressed in skeletal muscle following exercise [ 48 ] and has been shown to act in an anabolic fashion by increasing the production of myosin within skeletal muscles [ 49 ].

This response has been shown to be up-regulated by strength training [ 12 ]. It has therefore been proposed that IL acts to regulate the muscle to fat interactions which ultimately modulates the effects of exercise on the ratio of fat to lean body composition [ 51 ].

In addition to the levels of cytokines, the dynamic sequence following acute exercise also needs to be considered. The overall sequence of cytokine release in response to exercise involves an initial rise in the plasma concentration of IL-6, followed by a subsequent rise in the concentration of IL-1Ra, IL and soluble TNF-receptors TNF-R Fig.

This sequence of pro-inflammatory cytokines followed by release of anti-inflammatory cytokines is also seen in sepsis and acute inflammatory conditions but in contrast to sepsis, there is no preceding or accompanying increase in TNF-α in moderate acute exercise.

The acute changes in cytokine production during exercise are fairly well characterised, although there is some variation based on the intensity and type of exercise. However, less data is available on the long-term effects of regular exercise on the cytokine profile in humans.

The reasons for this include the difficulty in determining the extent to which the cytokine production is a consequence of physical fitness per se, associated lifestyle factors or a direct consequence of an exercise regime.

The existing studies indicate that the cytokine profile of an individual changes with chronic exercise, although the degree to which they change remains widely debated. With regards to changes in pro-inflammatory cytokines, the ATTICA study found that regular physical activity reduces basal plasma IL-6 and TNF-α in an urban population [ 52 ].

One proposed mechanism for the cytokine changes observed is that regular exercise leads to a reduction in body fat. Adipocytes are a major source of pro-inflammatory cytokines, including TNF-α and IL-6 [ 53 ], although this reduction also occurs in the absence of weight loss or changes in body composition, suggesting other mechanisms, including potentially also direct anti-inflammatory effects on immune cells, are likely to be involved [ 54 ].

Alongside the observed reduction in pro-inflammatory cytokines, regular exercise has been shown to increase the circulating concentration of anti-inflammatory cytokines.

Prokopchuk et al. demonstrated that IL-1Ra, IL-4 and IL were significantly increased with high-intensity training over a 6-week period [ 41 ], with the increase in IL-1Ra replicated by Forti et al. These findings support a relationship between low physical activity and inflammation, in which low levels of physical activity are associated with chronic low-grade inflammation, which may contribute to the increased cardiovascular risk associated with sedentary lifestyles [ 52 , 56 , 57 , 58 , 59 ].

This relationship between regular exercise, cytokine profiles and inflammation is one which, with further research, may provide further insight into the long-term benefits of exercise, particularly in regards to inflammatory, cardiovascular and other chronic diseases, and deliver additional opportunities to intervene in these conditions.

As mentioned, there are a multitude of undeniable benefits that regular, moderate exercise can provide, extending from metabolic to cardiac to psychological.

However, exercise is not without its dangers as well, especially when performed to an excessive level. Excluding injury, there are several levels of severity to the harm exercise can cause. Overtraining syndrome OTS is more severe, when the deterioration in performance persists despite adequate rest [ 94 , 98 ].

This is also associated with an array of other symptoms, including but not limited to: increased susceptibility to injury, fatigue, sleep disruption, weight loss, muscle tenderness, weakness, depression, anxiety, difficulty concentrating and loss of appetite.

In addition to this, there are biochemical and immunological changes which occur, with many reportedly experiencing an increased susceptibility to infection and illness [ 94 , 98 , ]. There are many proposed mechanisms for this, but thus far, no overarching explanation for the phenomenon seems to have been discovered.

It has been reported extensively that excessive exercise leads to an increase in pro-inflammatory cytokines [ 91 , 92 , 94 , 98 , 99 , , , , ]. Excessive exercise, particularly with the use of eccentric contractions often demonstrated using methods such as downhill running have been shown to increase pro-inflammatory cytokines in the serum, within the muscle tissue itself, and within articular cartilage [ , ].

It is plausible, and in fact likely that these cytokines are responsible for many of the symptoms experienced in OTS, such as low mood, loss of appetite, elevated cortisol levels etc.

However, studies have demonstrated that within 2 weeks of OTS diagnosis, pro-inflammatory cytokine levels normalised with rest whilst diminished performance levels remained, suggesting other processes are also at work [ ].

Many other mechanisms have been shown to contribute to varying degrees, including muscle glycogen depletion, free radical damage to contractile proteins, reduced mitochondrial capacity and so on [ 94 , 98 , ].

Tightly regulated inflammation is the process which enables this and involves myeloid cell invasion of the damaged muscle [ , , ]. Macrophages are the main component of this adaptive response, and cytokines thought to play a role in this include TNF-α and IFNγ, which cause a pro-inflammatory macrophage response, and IL-4, IL and IL, which cause an anti-inflammatory macrophage response and actually inhibit optimal repair [ ].

When adequate recovery is not allowed, chronic inflammation can set in, characterised by elevated intramuscular levels of TNF-α, IFNγ, IL-6 and IL, with muscle damage persisting for weeks [ 98 , ]. Chronically elevated IL-6 is known to downregulate expression of proteins involved in the mitochondrial electron transfer chain as well as upregulate oxidative ability of neutrophils, releasing more reactive oxygen species ROS causing free-radical damage to the contractile protein filaments within myofibrils, thus impeding muscle function [ 98 , ].

Intimately interlinked with the cytokines are the white blood cells. Nieman introduced the J-shaped curve in , suggesting that moderate exercise reduces the chance of infection whilst excessive exercise increases the risk above that of a sedentary individual [ ].

The infection in question is an upper respiratory tract infection URTI , since this is the most common infection experienced by athletes in both summer and winter sports [ ]. Exercise in moderate amounts is known to be immunoprotective [ 97 ]. In response to an acute bout of strenuous exercise e.

running a marathon , many immune cell changes are witnessed. These changes may last anywhere from h or beyond and are often proportional in magnitude and duration to the intensity and length of the exercise [ 99 ].

It is hypothesised that these changes, when compounded during an intense period of training without adequate rest, lead to overall immunosuppression and hence create the J-shape curve where high exercise levels lead to increased infections [ ].

Several controversies still remain unsolved regarding this issue, as the clinical significance of the initial immune changes remain contested. Some papers argue that a single bout of excessive exercise leads to increased URTI risk, such as Nieman who found increased URTI rates in those who participated in the Los Angeles Marathon, with the risk 2-times higher in those who trained over 97 km per week in the lead up to the race [ ].

It should be pointed out though that only 1 in 7 experienced any symptoms, so the vast majority did not [ ]. This may be related to the findings that high exercise loads, in addition to causing inflammation, also increase circulating concentrations of the anti-inflammatory cytokines IL-4 and IL, which are known to cause immunosuppression and correlate with increased URTI incidence [ , , , ].

Others, however, argue that the symptoms are in fact reactivation of a virus not completely cleared before running the race, or even non-infective inflammation as a result of increased exposure to irritants and pollutants whilst exercising [ 99 , , ].

In most studies, none of the infections were clinically diagnosed or verified using viral swabs, relying solely on the self-reporting and self-diagnosis of participants [ 97 ]. Other factors, such as pathogen exposure, psychological stress, sleep hygiene and diet were not taken into account, which are also known to have an effect on immune function [ 97 , ].

Whilst it is generally accepted that OTS has an associated infection risk, with these infections arriving more frequently and lasting longer than healthy individuals, the J-shape curve theory weakens when elite athletes are taken into consideration [ , , , ].

This makes sense, as Mårtensson et al. point out that in order to maintain a competitive training schedule of — h per year, athletes cannot afford to be stricken with illness very often [ ]. When extrapolating this data out, the curve becomes more of an S-shape, suggesting that the high level of activity associated with immunosuppression be more applicable to recreational and sub-elite athletes rather than professional, elite athletes [ , , , ].

As described, exercise-related cytokines are largely derived from within the musculoskeletal system therefore have a role to play in musculoskeletal health and its pathology.

Alongside this, many musculoskeletal conditions are characterised by local or systemic inflammation which, in turn, creates a complex relationship between the pre-existing immune environment and the additional immune modulation derived from exercise. In terms of pathophysiology, OA is the result of a disruption to the homeostatic process of synthesis and degradation of articular cartilage, extracellular matrix and subchondral bone.

OA commonly affects the knees, hips and small joints of the hands [ 60 ] and can result in significant pain and morbidity for patients.

It is estimated that 8. Treatment options include analgesia and physiotherapy in the earlier stages, although a significant number of patients will progress to requiring total joint replacement to improve their quality of life [ 62 ].

While osteoarthritis is not traditionally considered an inflammatory disease, the role of local cytokines in the pathophysiology of the condition has become increasingly recognised in recent years. Studies have found evidence of elevated IL-1 family members, TNF-α and IL-6 in the synovium, subchondral bone and cartilage of patients with OA, suggesting a role for inflammation in this pathology [ 63 , 64 ].

These cytokines are released by cells in adipose tissue and act as part of the system to negatively regulate cartilage synthesis. IL-1 and IL-6 inhibit collagen II synthesis while increasing the activity of matrix-metalloprotinases MMPs — collagen digesting enzymes.

The discovery of the role of IL-6 in cartilage regulation has prompted research into the effects of IL-6 blockade in OA [ 63 ].

A phase 3 clinical trial has recently been completed which examined the efficacy of tocilizumab, an IL-6 receptor inhibitor, in the treatment of OA [ 65 ]. The results from this trial are yet to be published, but they may provide further insight into the extent IL-6 influences OA pathology.

With relation to exercise, there has been extensive research into how exercise influences outcomes in OA. Meta-analyses have reported that exercise improves pain, function and quality of life for patients with OA [ 66 ] and in the UK the National Institute for Health and Care Excellence NICE guidelines recommend exercise therapy as part of first line treatment [ 62 ].

Despite these recommendations, little research is available to indicate how exercise improves OA at the molecular level. Data from the ADAPT trial showed that higher levels of inflammatory markers, including IL-6, are associated with poorer patient-reported outcomes, independent of body mass index [ 64 ].

However, a causal link has not been proven. Further research is warranted to determine the role of exercise-induced cytokines in the pathophysiology and treatment of OA, which may provide an evidence base for the best use of exercise in the management of OA.

A similar relationship can be seen in rheumatoid arthritis RA , the most prevalent form of inflammatory arthritis. RA is a systemic auto-immune condition that primarily affects the synovial joints.

RA is characterised by synovitis, autoantibody production, cartilage and bone destruction in addition to systemic inflammation and features such as cardiovascular and pulmonary manifestations. Cytokines play a central role in the pathogenesis of RA.

Amongst others, TNF-α and IL-6 have been implicated as key drivers of the systemic inflammation observed in RA patients. It has been proposed that the dysregulated, persistent production of IL-6 contributes to the production of autoantibodies, local inflammation and systemic effects [ 68 ].

In contrast to its role in exercise, IL-6 is thought to be largely pro-inflammatory in RA. Inhibition of IL-6 using anti-IL-6 receptor antibody tocilizumab is an effective and widely used first-line biological therapy in the treatment of active moderate-to-severe RA [ 69 ].

Given that reducing systemic IL-6 is beneficial in RA, it would be reasonable to hypothesise that exercise, and its associated rise in IL-6, may potentially worsen the symptoms of RA.

However, multiple studies have shown that exercise programmes can reduce symptoms of pain and stiffness in patients with RA. Crucially there is no evidence to suggest that exercise exacerbates disease activity [ 71 ].

These findings indicate that exercise, both resistance and aerobic, should be included in the treatment of RA. This is reflected in clinical guidelines which recommend that patients with RA should participate in regular exercise [ 72 ] [ 73 ].

The question therefore remains, how does exercise—which is known to induce IL-6 production and release—result in benefits for patients with RA? The answer may come from the transient nature of IL-6 release in exercise and lack of accompanying increase in TNF-α [ 74 ].

Unlike in active RA where IL-6 is chronically elevated, IL-6 rises throughout the period of exercise, before rapid removal from the circulation in the post-exercise period Fig.

During its short period of activity, IL-6 induces the upregulation of anti-inflammatory cytokines, including IL-1Ra, which persist in the circulation and induce a longer lasting anti-inflammatory effect [ 31 ]. The overall net anti-inflammatory effect of exercise may account for some of the symptomatic improvement for patients with RA, despite an accompanying increase in IL Exercise has also been recognised as beneficial for symptomatic management in patients with Psoriatic Arthritis PsA.

PsA is a chronic inflammatory joint disease, affecting joints, tendons and ligaments in some patients with skin psoriasis [ 76 ]. Whilst PsA can present similarly to RA, PsA represents a distinct immunopathology with a cytokine profile that is distinct from RA [ 77 ].

IL-6 is elevated in the synovium of patients with PsA and has a role in promoting T-helper cell differentiation, thus propagating the inflammatory cycle. The failure of IL-6 blockade suggests that, although IL-6 is involved, it is not central to the initiation of the inflammatory response [ 81 ].

It has been proposed that the inhibition of IL-6 leads to the overproduction of other pro-inflammatory cytokines, such as IL, locally within the skin and joints further driving pathology [ 82 ]. It is unclear whether the benefit of exercise in PsA is also due to the net anti-inflammatory effect proposed for RA or if low levels of IL-6 may help stabilise some of the other pro-inflammatory cytokines in affected tissues.

Tendinopathy is a common musculoskeletal presentation in both the general practice and orthopaedic setting. The condition can cause significant pain on movement and loss of function for patients, as well as weakening of the tendon itself [ 83 ].

This results in a predisposition to tears which may require surgical intervention. Current treatment for tendinopathy is centred around tendon loading programs to restore the capacity of the affected tendon; however, while this has been shown to be of benefit, for many patients loading programs fail to achieve adequate improvements, with the result many patients continue to suffer from chronic pain and dysfunction.

The role of inflammatory cytokines in tendinopathy has been widely debated; however, it is increasingly recognised as playing a significant role in the early stages of tendon disease [ 84 ]. As tendinopathy is most commonly a result of overuse, it often affects people who exercise regularly.

It is therefore of interest to determine how exercise-induced cytokines influence tendinopathy. As in skeletal muscle, exercise induces IL-6 expression in tendon tissue.

It has been shown that following exercise, IL-6 is upregulated in healthy tendon but not in tendinopathic tendon [ 85 ]. Additionally, mice lacking the IL-6 gene were found to have inferior tendon healing compared to wild-type mice [ 86 ].

This provides evidence for the role of exercise-induced cytokines in normal tendon physiology and adaptation to exercise, and suggests a role for IL-6 in tendon healing and failed response to loading stimuli.

Studies have shown that the use of eccentric loading exercises improve outcomes in patients with tendinopathy [ 87 ]. Recently, meta-analysis has found strong and consistent evidence indicating eccentric loading exercises are the most effective treatment for tendinopathies [ 88 ].

Additionally, it was found that eccentric exercise increases the cross-sectional area and stiffness of tendon [ 89 ]. Tendon tissue has been shown to upregulate IL-6 and TGF-β in response to mechanical stimulation, with TGF-β proposed as the driving force behind the structural changes observed with repeated eccentric exercise.

TGF-β has been shown to induce remodelling in a variety of tissues by promoting epithelial-mesenchymal transformation, suggesting this may also be the case in tendon [ 89 ].

Further research is required to understand the physiological role of IL-6 and TGF-β in tendons in order to help determine the point at which exercise begins to promote an inflammatory environment. Currently exercise is mainly used for symptom control and functional improvement in these conditions; an improved understanding of the relationship between exercise-related immune changes and musculoskeletal health may facilitate evidence-based therapeutic exercise strategies targeting the inflammatory pathology of these conditions, in conjunction with pharmaceutical agents.

Exercise induces significant physiological changes in the immune system, including characteristic cytokine responses. Most notable is a marked elevation in muscle-derived IL-6 which, despite being traditionally regarded as a potent pro-inflammatory cytokine, helps orchestrate an anti-inflammatory immune response in exercise.

Despite IL-6 and pro-inflammatory cytokines being implicated in various chronic musculoskeletal conditions, this exercise-induced increase in IL-6 does not appear to lead to inflammatory exacerbations in these conditions, with exercise generally conferring beneficial effects.

This interaction raises intriguing questions about how to best utilize this effect for the treatment of these conditions and offers exciting research opportunities within the fields of sports medicine and immunobiology, both clinically and experimentally. With continued research, exercise and its associated cytokine profile may provide an effective therapeutic avenue that will lessen the burden of musculoskeletal disease.

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Position statement. Part one: Immune function and exercise. Exercise Immunology Reviews, 17 , 6 — Widdowson , M. Are noroviruses emerging? Emerging Infectious Diseases, 11 , — Nieman is with the Human Performance Lab, Appalachian State University, Kannapolis, NC.

Peeling is with the School of Human Sciences Exercise and Sport Science , The University of Western Australia, Crawley, Western Australia.

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Patel , A. Gastrointestinal prophylaxis in sports medicine. Sports Health, 10 2 , — Peake , J. Muscle damage and inflammation during recovery from exercise. Journal of Applied Physiology, , — Pedlar , C. Iron balance and iron supplementation for the female athlete: A practical approach.

European Journal of Sports Science, 18 2 , — Peeling , P. Sports foods and dietary supplements for optimal function and performance enhancement in track and field athletes.

International Journal of Sport Nutrition and Exercise Metabolism, 29 2. Athletic induced iron deficiency: New insights into the role of inflammation, cytokines and hormones. European Journal of Applied Physiology, 4 , — Effects of exercise on hepcidin response and iron metabolism during recovery.

International Journal of Sport Nutrition and Exercise Metabolism, 19 6 , — Peters , E. Ultramarathon running and upper respiratory tract infections. An epidemiological survey.

South African Medical Journal, 64 , — Rampton , D. Weiss , G. Hypersensitivity reactions to intravenous iron: Guidance for risk minimization and management.

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Are noroviruses emerging? Emerging Infectious Diseases, 11 , — Nieman is with the Human Performance Lab, Appalachian State University, Kannapolis, NC. Peeling is with the School of Human Sciences Exercise and Sport Science , The University of Western Australia, Crawley, Western Australia.

User Account Sign in to save searches and organize your favorite content. Not registered? Sign up My Content 0 Recently viewed 0 Save Entry. Recently viewed 0 Save Search. Human Kinetics. Previous Article Next Article. Exercise-Induced Illness and Inflammation: Can Immunonutrition and Iron Help?

in International Journal of Sport Nutrition and Exercise Metabolism. Lindy M. Castell Lindy M. Castell University of Oxford Search for other papers by Lindy M.

Castell in Current site Google Scholar PubMed Close. David C. Nieman David C. Nieman Appalachian State University Search for other papers by David C. Nieman in Current site Google Scholar PubMed Close.

Stéphane Bermon Stéphane Bermon International Association of Athletics Federations Search for other papers by Stéphane Bermon in Current site Google Scholar PubMed Close. Peter Peeling Peter Peeling The University of Western Australia Search for other papers by Peter Peeling in Current site Google Scholar PubMed Close.

In Print: Volume Issue 2. Page Range: — Open access. Get Citation Alerts. Download PDF. Abstract Full Text PDF Author Notes. Immunodepression and Immunonutrition Investigation of exercise-induced effects on the immune system began more than years ago, when Larrabee observed a marked leukocytosis after violent exercise, including a large number of polymorphonuclear neutrophils.

Illness Risk Subclinical and Clinical Illness As a consequence of exercise-induced immunodepression, resistance to pathogens is lowered, increasing the risk of subclinical and clinical infection and illness Schwellnus et al.

Figure 1 —The incidence of illness in sedentary controls and athletes: This is reduced i. Training the gut During recent years, some promising research has also shown that the stomach and the gut can be trained to improve tolerance and gastric emptying during exercise see Jeukendrup, for a more detailed description.

Immunonutrition Increasing numbers of studies involving elite athletes and immunonutrition have been reported. Practical Recommendations 1. Training and Competition Load Management a. Develop a detailed, individualized training and competition plan that also provides for sufficient recovery using sleep, nutrition, hydration, and psychological strategies.

Develop a competition event calendar based on the health of individual athletes. Monitor for early signs and symptoms of overreaching, overtraining, and illness. Avoid intensive training when ill or experiencing early signs and symptoms of illness. Participate in current illness surveillance systems by sport agencies.

Hygienic, Lifestyle, Nutritional, and Behavioral Strategies a. Minimize pathogen exposure by avoiding close contact with infected individuals in crowded, enclosed spaces and not sharing drinking or eating implements.

Medical staff should isolate infected athletes. Limit hand-to-face contact i. Medical staff should educate athletes to minimize pathogen spread to others e. Follow other hygienic practices to limit all types of infections, including safe sex and the use of condoms.

Wear open footwear when using public facilities, to limit skin infections. Use insect repellent and cover the arms and legs with clothing at dawn or dusk. Maintain vaccines needed for home and foreign travel; focus on annual influenza vaccination.

As advised in the section on gastrointestinal illness, during foreign travel, all team members should minimize risks by drinking from sealed bottles. They should also avoid foods such as unpeeled fresh fruits and vegetables, open buffets, undercooked meats, and foods from street vendors.

Follow strategies that facilitate regular, high-quality sleep. Avoid excessive alcohol intake. Consume a well-balanced diet with sufficient energy to maintain a healthy weight; focus on grains, fruits, and vegetables to provide sufficient CHO and polyphenols that reduce exercise-induced inflammation and improve viral protection see Bermon et al.

Psychological Load Management a. Follow stress management techniques that reduce the extraneous load of life hassles and stresses. Develop coping strategies that minimize the internalized impact of negative life events and emotions.

Periodically monitor psychological stresses using available instruments. Conclusion Athletes must train hard for competition, and they are interested in strategies to keep their immune systems robust and illness rates low despite the physiological stress experienced.

Crossref Brittenham , G. Crossref Castell , L. PubMed ID: Larrabee , R. PubMed ID: false. PubMed ID: Nieman , D. Crossref Peeling , P. PubMed ID: Peters , E. Address author correspondence to Lindy M. Castell at lindy. castell gtc. Save Cite Email this content Share Link Copy this link, or click below to email it to a friend.

xml The link was not copied. Your current browser may not support copying via this button. International Journal of Sport Nutrition and Exercise Metabolism. Exercise did seem to produce an anti-inflammatory cellular response, which could be seen in the reduction of the cytokine TNF.

Although the anti-inflammatory benefits of physical activity are already known to researchers, Hong explains, this study explains the process in more detail. The lead author also highlights the importance of this study for people with reduced strength or mobility who are under the impression that physical exercise needs to be extremely intense in order to be effective.

Twenty minutes to half an hour of moderate exercise, including fast walking, appears to be sufficient. Feeling like a workout needs to be at a peak exertion level for a long duration can intimidate those who suffer from chronic inflammatory diseases and could greatly benefit from physical activity.

Learn why weekend exercise may be just as good as being active every day. Researchers have found that high-intensity interval training prompts a rise in the release of endorphins in the brain, compared with less intense….

Aerobic exercises and those that incorporate high intensity interval training can all burn a significant number of calories. Learn more in this…. According to a study published in the American Journal of Physiology, 30 minutes of daily exercise is just as effective for losing weight as 60….

More time spent in light-intensity physical activity and less being sedentary is tied to lower risk of all-cause and cardiovascular death, new study…. People who exercise and eat a healthy diet have the lowest risk of mortality and death from cardiovascular disease and certain cancers, a new study….

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Medical News Today. Health Conditions Health Products Discover Tools Connect. Just 20 minutes of exercise enough to reduce inflammation, study finds. Effects of resistance training at different loads on inflammatory markers in young adults.

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de Vries JE. Immunosuppressive and anti-inflammatory properties of interleukin Ann Med. Ekblom B, Ekblom Ö, Malm C. Infectious episodes before and after a marathon race. Download references. Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences, University of Glasgow, University Avenue, Glasgow, G12 8TA, Scotland, UK.

Sophie Docherty, Rachael Harley, Joseph J. McAuley, Lindsay A. School of Physiotherapy, Royal College of Surgeons in Ireland, Dublin, Ireland. Physiotherapy Department, Connolly Hospital, Dublin, Ireland. You can also search for this author in PubMed Google Scholar.

NLM, PDK, SS, LC and CP provided expert advice. SD, RH, JJ. M analysed the data. All authors wrote the paper. All authors read and approved the final manuscript. Correspondence to Neal L. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Reprints and permissions. Docherty, S. et al. The effect of exercise on cytokines: implications for musculoskeletal health: a narrative review.

BMC Sports Sci Med Rehabil 14 , 5 Download citation. Received : 07 September Accepted : 31 December Published : 06 January Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Review Open access Published: 06 January The effect of exercise on cytokines: implications for musculoskeletal health: a narrative review Sophie Docherty 1 na1 , Rachael Harley 1 na1 , Joseph J.

McAuley 1 , Lindsay A. Crowe 1 , Carles Pedret 2 , Paul D. Millar ORCID: orcid. Abstract The physiological effects of physical exercise are ubiquitously reported as beneficial to the cardiovascular and musculoskeletal systems.

What this review shows Activation of the innate immune system occurs in response to exercise and it is proposed this is largely mediated by cytokine signalling.

Background A prima facia case for the benefits of physical exercise is now largely undisputed [ 1 ]. Cytokines in acute exercise The first study suggesting an exercise induced cytokine response was published in by Cannon and Kluger [ 5 ].

IL-6 The response of IL-6 to exercise has been studied extensively in the scientific community and considered the pivotal cytokine in exercise physiology [ 3 , 11 , 12 , 13 ].

Role of IL-6 in inflammation and exercise IL-6 is a pleiotropic cytokine with a broad range of functions in immunoregulation, haematopoiesis and inflammation [ 14 ]. Table 1 Summary of the roles of key cytokines in relation to exercise Full size table. Illustration of the actions of exercise-derived IL-6 on local and systemic metabolism.

Full size image. Illustration of circulating cytokines released in response to exercise. Conclusions Exercise induces significant physiological changes in the immune system, including characteristic cytokine responses.

Availability of data and materials N. M has access to all the data and data are available upon request. Abbreviations NK: Natural killer cell kDA: Kilodalton IL: Interleukin IL-1Ra: Interleukin-1 receptor antagonist Gp Glycoprotein TNF: Tumour necrosis factor AMPK: AMP-activated protein kinase GLUT: Glucose transporter T H 1: T-helper 1 cell T H 2: T-helper 2 cell mRNA: Messenger RNA OTS: Overtraining syndrome IFN: Interferon ROS: Reactive oxygen species URTI: Upper respiratory tract infection IgA: Immunoglobulin A MHC: Major histocompatibility complex OA: Osteoarthritis MMP: Matrix-metalloproteinase NICE: National Institute for Clinical Excellence RA: Rheumatoid arthritis PsA: Psoriatic arthritis.

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Further analyses showed that in both groups, Tregs lowered exercise-induced inflammation. None of those changes were seen in the muscle cells of sedentary mice.

However, the metabolic and performance benefits of exercise were apparent only in the regular exercisers — the mice that had repeated bouts of running.

In that group, Tregs not only subdued exertion-induced inflammation and muscle damage, but also altered muscle metabolism and muscle performance, the experiments showed. This finding aligns with well-established observations in humans that a single bout of exercise does not lead to significant improvements in performance and that regular activity over time is needed to yield benefits.

The hind leg muscles of mice lacking Treg cells right showed prominent signs of inflammation after regular exercise, compared with those from mice with intact Tregs left.

The research showed such that this uncontrolled inflammation negatively impacted muscle metabolism and function. Further analyses confirmed that Tregs were, indeed, responsible for the broader benefits seen in regular exercisers.

Animals that lacked Tregs had unrestrained muscle inflammation, marked by the rapid accumulation of inflammation-promoting cells in their hind leg muscles. Their muscle cells also had strikingly swollen mitochondria, a sign of metabolic abnormality.

More importantly, animals lacking Tregs did not adapt to increasing demands of exercise over time the way mice with intact Tregs did. They did not derive the same whole-body benefits from exercise and had diminished aerobic fitness.

Further analyses revealed that interferon acts directly on muscle fibers to alter mitochondrial function and limit energy production. Blocking interferon prevented metabolic abnormalities and improved aerobic fitness in mice lacking Tregs. Interferon is known to promote chronic inflammation, a process that underlies many chronic diseases and age-related conditions and has become a tantalizing target for therapies aimed at reducing inflammation.

Tregs have also captured the attention of scientists and industry as treatments for a range of immunologic conditions marked by abnormal inflammation. There are efforts afoot to design interventions targeting Tregs in the context of specific immune-mediated diseases.

And while immunologic conditions driven by aberrant inflammation require carefully calibrated therapies, exercise is yet another way to counter inflammation, the researchers said. Co-investigators included Yizhi Sun, Birgitta Ryback, Bruce Spiegelman, Amber Mueller, and Christophe Benoist.

The work was funded by National Institutes of Health grants R01 AR, F32 AG, and F32 AG; and by the JPB Foundation. Hope for progress even after a foot fall, trial shows, defying pessimism that hurts research and families. Experts weigh in on pop superstar's cultural and financial impact as her tours and albums continue to break records.

Understanding the molecular underpinnings of exercise Protecting from cardiovascular disease, reducing the risk of diabetes, shielding against dementia. T cell heroes and inflammation-fueling villains Exercise is known to cause temporary damage to the muscles, unleashing a cascade of inflammatory responses.

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Feeling like a workout needs to be at a peak exertion level for a long duration can intimidate those who suffer from chronic inflammatory diseases and could greatly benefit from physical activity. Learn why weekend exercise may be just as good as being active every day.

Researchers have found that high-intensity interval training prompts a rise in the release of endorphins in the brain, compared with less intense…. Aerobic exercises and those that incorporate high intensity interval training can all burn a significant number of calories.

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More time spent in light-intensity physical activity and less being sedentary is tied to lower risk of all-cause and cardiovascular death, new study…. People who exercise and eat a healthy diet have the lowest risk of mortality and death from cardiovascular disease and certain cancers, a new study….

My podcast changed me Can 'biological race' explain disparities in health? Why Parkinson's research is zooming in on the gut Tools General Health Drugs A-Z Health Hubs Health Tools Find a Doctor BMI Calculators and Charts Blood Pressure Chart: Ranges and Guide Breast Cancer: Self-Examination Guide Sleep Calculator Quizzes RA Myths vs Facts Type 2 Diabetes: Managing Blood Sugar Ankylosing Spondylitis Pain: Fact or Fiction Connect About Medical News Today Who We Are Our Editorial Process Content Integrity Conscious Language Newsletters Sign Up Follow Us.

Medical News Today. Health Conditions Health Products Discover Tools Connect. Just 20 minutes of exercise enough to reduce inflammation, study finds. By Ana Sandoiu on January 16, As little as 20 minutes of exercise reduces inflammation.

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