PERSISTENT LOW-GRADE INFLAMMATION, as indicated by higher circulating levels of inflammatory mediators such as C-reactive protein, interleukin-6 and tumour necrosis factor-α, is a strong risk factor for several chronic diseases. There are data indicating that decreasing energy intake and increasing physical activity may be effective therapies for reducing overall inflammation. Evidence is strong that circulating levels of inflammatory markers are elevated with total and abdominal obesity, possibly owing to a higher secretion rate of cytokines by adipose tissue in obese people. Moreover, very-low-energy dietary weight loss reduces both circulating markers of inflammation and adipose-tissue cytokine production. Data from several large population-based cohorts show an inverse association between markers of systemic inflammation and physical activity or fitness status; small-scale intervention studies support that exercise training diminishes inflammation. Dietary weight loss plus exercise is likely more effective than weight reduction alone in reducing inflammation. To date, data from randomized, controlled trails designed to definitively test the effects of weight loss or exercise training, or both, on inflammation are limited. Future studies are required to define the amount of weight loss needed for clinically meaningful reductions of inflammation; in addition, fully powered and controlled studies are necessary to clarify the effect of exercise training on chronic, systemic inflammation.
Regular exercise is positively associated with health. It has also been suggested to exert anti-inflammatory effects. In healthy subjects, a single exercise session results in immune cell activation, which is characterized by production of immune modulatory peptides (e.g. IL-6, IL-8), a leukocytosis and enhanced immune cell functions. Upon cessation of exercise, immune activation is followed by a tolerizing phase, characterized by a reduced responsiveness of immune cells. Regular exercise of moderate intensity and duration has been shown to exert anti-inflammatory effects and is associated with a reduced disease incidence and viral infection susceptibility. Specific exercise programs may therefore be used to modify the course of chronic inflammatory and infectious diseases such as cystic fibrosis (CF).
Patients with CF suffer from severe and chronic pulmonary infections and inflammation, leading to obstructive and restrictive pulmonary disease, exercise intolerance and muscle cachexia. Inflammation is characterized by a hyper-inflammatory phenotype. Patients are encouraged to engage in exercise programs to maintain physical fitness, quality of life, pulmonary function and health.
In this review, we present an overview of available literature describing the association between regular exercise, inflammation and infection susceptibility and discuss the implications of these observations for prevention and treatment of inflammation and infection susceptibility in patients with CF.
Cytokines; Exercise; Immune system; Infection; Inflammation; Lung disease; Respiratory system
An increase in the prevalence of obesity in people with spinal cord injury can contribute to low-grade chronic inflammation and increase the risk of infection in this population. A decrease in sympathetic activity contributes to immunosuppression due to the lower activation of immune cells in the blood. The effects of physical exercise on inflammatory parameters in individuals with spinal cord injury have not been well described. We conducted a review of the literature published from 1974 to 2012. This review explored the relationships between low-grade inflammation, spinal cord injury, and exercise to discuss a novel mechanism that might explain the beneficial effects of exercise involving an increase in catecholamines and cytokines in people with spinal cord injury.
There are few studies evaluating exercise in the nondialysis chronic kidney disease (CKD) population. This review covers the rationale for exercise among patients with CKD not requiring dialysis and the effects of exercise training on physical functioning, progression of kidney disease, and cardiovascular risk factors. In addition, we address the issue of the risk of exercise and make recommendations for implementation of exercise in this population.
Evidence from uncontrolled studies and from small randomized controlled trials shows that exercise training results in improved physical performance and functioning among patients with CKD. In addition, although there are no studies examining cardiovascular outcomes, several studies suggest that cardiovascular risk factors such as hypertension, inflammation, and oxidative stress, may be improved with exercise training in this population. Although the current literature does not allow for definitive conclusions about whether exercise training slows the progression of kidney disease, no study has reported worsening of kidney function as a result of exercise training. In the absence of guidelines specific to the CKD population, recent guidelines developed for older individuals and patients with chronic disease should be applied to the CKD population.
In sum, exercise appears to be safe in this patient population if begun at moderate intensity and increased gradually. Indeed, the evidence suggests that the risk of remaining inactive is higher. Patients should be advised to increase their physical activity when possible and referred to physical therapy or cardiac rehabilitation programs when appropriate.
This paper aims to highlight the importance of exercise in patients with rheumatoid arthritis (RA) and to demonstrate the multitude of beneficial effects that properly designed exercise training has in this population. RA is a chronic, systemic, autoimmune disease characterised by decrements to joint health including joint pain and inflammation, fatigue, increased incidence and progression of cardiovascular disease, and accelerated loss of muscle mass, that is, “rheumatoid cachexia”. These factors contribute to functional limitation, disability, comorbidities, and reduced quality of life. Exercise training for RA patients has been shown to be efficacious in reversing cachexia and substantially improving function without exacerbating disease activity and is likely to reduce cardiovascular risk. Thus, all RA patients should be encouraged to include aerobic and resistance exercise training as part of routine care. Understanding the perceptions of RA patients and health professionals to exercise is key to patients initiating and adhering to effective exercise training.
Persons at any age can substantially improve their fitness for work and play through appropriate exercise training. Considerable evidence indicates that physical activity is valuable for weight control, modifying lipids and improving carbohydrate tolerance. Less rigorous scientific data are available for associated long-term blood pressure and psychological changes with habitual exercise. Strenuous physical activity most likely reduces the incidence of coronary heart disease and the detrimental impact of certain chronic diseases on health. Adverse effects may result from a training program, but the major concern is the susceptibility to cardiovascular events during and immediately after exertion. To achieve optimal benefits with minimal risk, exercise must be carefully prescribed within the context of overall health and training objectives. Taken altogether, a distinct rationale exists for regular vigorous exercise as an integral part of a personal health maintenance program.
Persistent, sub-clinical inflammation, as indicated by higher circulating levels of inflammatory mediators, is a prominent risk factor for several chronic diseases, as well as aging-related disability. As such, the inflammatory pathway is a potential therapeutic target for lifestyle interventions designed to reduce disease and disability. Physical exercise is well recognized as an important strategy for reducing the risk of chronic disease, and recent research has focused on its role in the improvement of the inflammatory profile. This review summarizes the evidence for and against the role of increasing physical activity in the reduction of chronic inflammation. Large population-based cohort studies consistently show an inverse association between markers of systemic inflammation and physical activity or fitness status, and data from several small-scale intervention studies support that exercise training diminishes inflammation. However, data from large, randomized, controlled trials designed to definitively test the effects of exercise training on inflammation are limited, and results are inconclusive. Future studies are needed to refine our understanding of the effects of exercise training on systemic low-grade inflammation, the magnitude of such an effect, and the amount of exercise necessary to elicit clinically meaningful changes in the deleterious association between inflammation and disease.
inflammation; exercise; cytokines; acute phase proteins; physical activity
Chronic inflammation is involved in the pathogenesis of insulin resistance, atherosclerosis, neurodegeneration, and tumour growth. Regular exercise offers protection against type 2 diabetes, cardiovascular diseases, colon cancer, breast cancer, and dementia. Evidence suggests that the protective effect of exercise may to some extent be ascribed to the antiinflammatory effect of regular exercise. Here we suggest that exercise may exert its anti-inflammatory effect via a reduction in visceral fat mass and/or by induction of an anti-inflammatory environment with each bout of exercise. According to our theory, such effects may in part be mediated via muscle-derived peptides, so-called “myokines”. Contracting skeletal muscles release myokines with endocrine effects, mediating direct anti-inflammatory effects, and/or specific effects on visceral fat. Other myokines work locally within the muscle and exert their effects on signalling pathways involved in fat oxidation and glucose uptake. By mediating anti-inflammatory effects in the muscle itself, myokines may also counteract TNF-driven insulin resistance. In conclusion, exercise-induced myokines appear to be involved in mediating both systemic as well as local anti-inflammatory effects.
Reaction time, coordination, and cognition performance typically diminish in older adults, which may lead to gait impairments, falls, and injuries. Regular strength–balance exercises are highly recommended to reduce this problem and to improve health, well-being, and independence in old age. However, many older people face a lack of motivation in addition to other strong barriers to exercise. We developed ActiveLifestyle, an information technology (IT)-based system for active and healthy aging aiming at improving balance and strength. ActiveLifestyle is a training app that runs on a tablet and assists, monitors, and motivates older people to follow personalized training plans autonomously at home.
The objectives were to (1) investigate which IT-mediated motivation strategies increase adherence to physical exercise training plans in older people, (2) assess the impact of ActiveLifestyle on physical activity behavior change, and (3) demonstrate the effectiveness of the ActiveLifestyle training to improve gait speed.
A total of 44 older adults followed personalized, 12-week strength and balance training plans. All participants performed the exercises autonomously at home. Questionnaires were used to assess the technological familiarity and stage of behavior change, as well as the effectiveness of the motivation instruments adopted by ActiveLifestyle. Adherence to the exercise plan was evaluated using performance data collected by the app and through information given by the participants during the study. Pretests and posttests were performed to evaluate gait speed of the participants before and after the study.
Participants were 75 years (SD 6), predominantly female (64%), held a trade or professional diploma (54%), and their past profession was in a sitting position (43%). Of the 44 participants who enrolled, 33 (75%) completed the study. The app proved to assist and motivate independently living and healthy older adults to autonomously perform strength–balance exercises (median 6 on a 7-point Likert scale). Social motivation strategies proved more effective than individual strategies to stimulate the participants to comply with the training plan, as well as to change their behavior permanently toward a more physically active lifestyle. The exercises were effective to improve preferred and fast gait speed.
ActiveLifestyle assisted and motivated independently living and healthy older people to autonomously perform strength–balance exercises over 12 weeks and had low dropout rates. The social motivation strategies were more effective to stimulate the participants to comply with the training plan and remain on the intervention. The adoption of assistive technology devices for physical intervention tends to motivate and retain older people exercising for longer periods of time.
motivation; exercises; aged; tablet; mobility; delivery of health care
Most of the human population in the western world has access to unlimited calories and leads an increasingly sedentary lifestyle. The propensity to undertake voluntary exercise or indulge in spontaneous physical exercise, which might be termed "exercise salience", is drawing increased scientific attention. Despite its genetic aspects, this complex behaviour is clearly modulated by the environment and influenced by physiological states. Inflammation is often overlooked as one of these conditions even though it is known to induce a state of reduced mobility. Chronic subclinical inflammation is associated with the metabolic syndrome; a largely lifestyle-induced disease which can lead to decreased exercise salience. The result is a vicious cycle that increases oxidative stress and reduces metabolic flexibility and perpetuates the disease state. In contrast, hormetic stimuli can induce an anti-inflammatory phenotype, thereby enhancing exercise salience, leading to greater biological fitness and improved functional longevity. One general consequence of hormesis is upregulation of mitochondrial function and resistance to oxidative stress. Examples of hormetic factors include calorie restriction, extreme environmental temperatures, physical activity and polyphenols. The hormetic modulation of inflammation, and thus, exercise salience, may help to explain the highly heterogeneous expression of voluntary exercise behaviour and therefore body composition phenotypes of humans living in similar obesogenic environments.
Chronic noncommunicable diseases (CNCDs), which include cardiovascular disease, some cancers, for example, colon cancer, breast cancer, and type 2 diabetes, are reaching epidemic proportions worldwide. It has now become clear that low-grade chronic inflammation is a key player in the pathogenesis of most CNCDs. Given that regular exercise offers protection against all causes of mortality, primarily by protection against atherosclerosis and insulin resistance, we suggest that exercise may exert some of its beneficial health effects by inducing anti-inflammatory actions. Recently, IL-6 was introduced as the first myokine, defined as a cytokine, which is produced and released by contracting skeletal muscle fibres, exerting its effects in other organs of the body. We suggest that skeletal muscle is an endocrine organ and that myokines may be involved in mediating the beneficial effects against CNCDs associated with low-grade inflammation.
Chronic gastro-oesophageal reflux disease and excessive body fat are considered principal causes of Barrett's oesophagus (a metaplastic change in the cells lining the oesophagus) and its neoplastic progression, oesophageal adenocarcinoma. Metabolic disturbances including altered levels of obesity-related cytokines, chronic inflammation and insulin resistance have also been associated with oesophageal cancer development, especially in males. Physical activity may have the potential to abrogate metabolic disturbances in males with Barrett's oesophagus and elicit beneficial reductions in body fat and gastro-oesophageal reflux symptoms. Thus, exercise may be an effective intervention in reducing oesophageal adenocarcinoma risk. However, to date this hypothesis remains untested.
The 'Exercise and the Prevention of Oesophageal Cancer Study' will determine whether 24 weeks of exercise training will lead to alterations in risk factors or biomarkers for oesophageal adenocarcinoma in males with Barrett's oesophagus. Our primary outcomes are serum concentrations of leptin, adiponectin, tumour necrosis factor-alpha, C-reactive protein and interleukin-6 as well as insulin resistance. Body composition, gastro-oesophageal reflux disease symptoms, cardiovascular fitness and muscular strength will also be assessed as secondary outcomes.
A randomized controlled trial of 80 overweight or obese, inactive males with Barrett's oesophagus will be conducted in Brisbane, Australia. Participants will be randomized to an intervention arm (60 minutes of moderate-intensity aerobic and resistance training, five days per week) or a control arm (45 minutes of stretching, five days per week) for 24 weeks. Primary and secondary endpoints will be measured at baseline (week 0), midpoint (week 12) and at the end of the intervention (week 24).
Due to the increasing incidence and very high mortality associated with oesophageal adenocarcinoma, interventions effective in preventing the progression of Barrett's oesophagus are urgently needed. We propose that exercise may be successful in reducing oesophageal adenocarcinoma risk. This primary prevention trial will also provide information on whether the protective association between physical activity and cancer is causal.
Physical inactivity leads to the accumulation of visceral fat and, consequently, to the activation of a network of inflammatory pathways which may promote development of insulin resistance, atherosclerosis, neurodegeneration, and tumour growth. These conditions belong to the “diseasome of physical inactivity”. In contrast, the protective effect of regular exercise against diseases associated with chronic inflammation may to some extent be ascribed to an anti-inflammatory effect. The so called “acute exercise threshold”, the complex mixture of several variables involved in exercise, such as type, volume, frequency, and intensity range is capable of inducing positive physiological adaptations and has been specifically addressed in the recent literature. The major concern is related to the level of the threshold: “exercise training shifts from a therapeutic adaptive intervention to one with potential pathological consequences”. Nonetheless, if the mechanical stimulus is too weak to disrupt cellular homeostasis, training adaptations will not occur. Answering these questions could present practical applications, especially during inflammatory diseases associated with detrimental muscle effects and could theoretically constitute a “new” therapeutic approach to treat/improve an inflammatory state. This paper aims to describe specific data from the literature regarding the effects of exercise on inflammatory diseases in order to promote a more sophisticated perspective on the anti-inflammatory effects of exercise.
Low-grade chronic inflammation is an important risk factor for age-related morbidity. Health behaviors, including average aggregate measures of sleep, have been linked to increased inflammation in older adults. Variability in sleep timing may also be associated with increased inflammation. This study evaluated relationships among several health behaviors and circulating proinflammatory cytokines (IL-6 and TNF-α).
Participants were community dwelling older adults >60 years (N = 222: 39 bereaved, 55 caregivers, 52 with insomnia, and 76 good sleepers). Mean values and intra-individual variability in sleep, as well as caffeine and alcohol use, exercise, and daytime napping were assessed by sleep diaries. Blood draws were obtained in the morning.
Several interactions were noted between sleep behaviors, inflammatory markers, and participant group. Greater variability in wake time and time in bed was associated with higher IL-6 among good sleepers relative to caregivers and older adults with insomnia. Good sleepers who consumed moderate amounts of alcohol had the lowest concentrations of IL-6 compared to the other three groups who consumed alcohol. Insomnia subjects, but not good sleepers, showed increased concentrations of IL-6 associated with caffeine use. Caregivers showed increased concentrations of TNF-α with alcohol use relative to good sleepers. Greater variability in bedtime, later wake times and longer time in bed was associated with higher TNF-α regardless of group.
Moderation and regularity in the practice of certain health behaviors, including sleep practices, were associated with lower plasma levels of inflammatory markers in older adults. Life circumstances and specific sleep disorders may modify these associations.
sleep variability; health-related behaviors; inflammatory markers; aging; caffeine; alcohol; cytokine; sleep timing
Aging is associated with low-grade inflammation. The benefits of regular exercise for the elderly are well established, whereas less is known about the impact of low-intensity resistance exercise on low-grade inflammation in the elderly. Twenty-one elderly women (mean age ± SD,
85.0 ± 4.5 years) participated in 12 weeks of resistance exercise training. Muscle thickness and circulating levels of C-reactive protein (CRP), serum amyloid A (SAA), heat shock protein (HSP)70, tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, monocyte chemotactic protein (MCP-1), insulin, insulin-like growth factor (IGF)-I, and vascular endothelial growth factor (VEGF) were measured before and after the exercise training. Training reduced the circulating levels of CRP, SAA (P < .05), HSP70, IGF-I, and insulin (P < .01). The training-induced reductions in CRP and TNF-α were significantly (P < .01, P < .05) associated with increased muscle thickness (r = −0.61, r = −0.54), respectively. None of the results were significant after applying a Bonferroni correction. Resistance training may assist in maintaining or improving muscle volume and reducing low-grade inflammation.
Hypertension is a ubiquitous and serious disease. Regular exercise has been recommended as a strategy for the prevention and treatment of hypertension because of its effects in reducing clinical blood pressure; however, ambulatory blood pressure is a better predictor of target-organ damage than clinical blood pressure, and therefore studying the effects of exercise on ambulatory blood pressure is important as well. Moreover, different kinds of exercise might produce distinct effects that might differ between normotensive and hypertensive subjects.
The aim of this study was to review the current literature on the acute and chronic effects of aerobic and resistance exercise on ambulatory blood pressure in normotensive and hypertensive subjects. It has been conclusively shown that a single episode of aerobic exercise reduces ambulatory blood pressure in hypertensive patients. Similarly, regular aerobic training also decreases ambulatory blood pressure in hypertensive individuals. In contrast, data on the effects of resistance exercise is both scarce and controversial. Nevertheless, studies suggest that resistance exercise might acutely decrease ambulatory blood pressure after exercise, and that this effect seems to be greater after low-intensity exercise and in patients receiving anti-hypertensive drugs. On the other hand, only two studies investigating resistance training in hypertensive patients have been conducted, and neither has demonstrated any hypotensive effect. Thus, based on current knowledge, aerobic training should be recommended to decrease ambulatory blood pressure in hypertensive individuals, while resistance exercise could be prescribed as a complementary strategy.
Exercise; Blood pressure; Hypertension; Physiology and Health
The objective of the present study was to investigate the changes in a large panel of emergent geriatric biomarkers in long-term trained elderly men to analyze the effects of long-term exercise on an aged population. We collected blood samples from two groups of male volunteers older than 65 years who maintain a measure of functional independence: one group of sedentary subjects without a history of regular physical activity and the other of subjects who have sustained training, starting during adulthood (mean training time = 49 ± 8 years). We studied morbidity, polypharmacy, cellular and serological inflammatory parameters, and endocrine mediators. After adjusting for confounding factors, we observed reduced medication intake per subject and lower number of diseases per subject with statistical differences nearly significant in the long-term exercise group. We showed that long-term training was associated with lower levels of white blood cell counts, neutrophil counts, interleukin-6, interleukin-10, interleukin-1 receptor antagonist, and soluble TNF receptor-I. Furthermore, we noted an increase in the concentrations of insulin-like growth factor-1 and dehydroepiandrosterone in the long-term training group. We concluded that long-term exercise training from adulthood to old age is clearly associated with a healthy profile of emergent geriatric biomarkers. Long-term training could improve the inflammatory–endocrine imbalance associated with disease, frailty, functional decline, and mortality in elderly men. Our results point to the benefits of prolonged exercise from adulthood to old age.
Aging; Long-term training; Exercise; Inflammatory biomarkers; Endocrine biomarkers; Life Sciences; Molecular Medicine; Geriatrics/Gerontology; Cell Biology
Resistance training (RT) is associated with reduced risk of low grade inflammation related diseases, such as cardiovascular disease and type 2 diabetes. The majority of the data studying cytokines and exercise comes from endurance exercise. In contrast, evidence establishing a relationship between RT and inflammation is more limited. This review focuses on the cytokine responses both following an acute bout, and after chronic RT. In addition, the effect of RT on low grade systemic inflammation such as individuals at risk for type 2 diabetes is reviewed. Cytokines are secreted proteins that influence the survival, proliferation, and differentiation of immune cells and other organ systems. Cytokines function as intracellular signals and almost all cells in the body either secrete them or have cytokine receptors. Thus, understanding cytokine role in a specific physiological situation such as a bout of RT can be exceedingly complex. The overall effect of long term RT appears to ameliorate inflammation, but the specific effects on the inflammatory cytokine, tumor necrosis factor alpha are not clear, requiring further research. Furthermore, it is critical to differentiate between chronically and acute Interleukin-6 levels and its sources. The intensity of the RT and the characteristics of the training protocol may exert singular cytokine responses and as a result different adaptations to exercise. More research is needed in the area of RT in healthy populations, specifically sorting out gender and age RT acute responses. More importantly, studies are needed in obese individuals who are at high risk of developing low grade systemic inflammatory related diseases. Assuring adherence to the RT program is essential to get the benefits after overcoming the first acute RT responses. Hence RT could be an effective way to prevent, and delay low grade systemic inflammatory related diseases.
Cytokines; IL-6; inflammatory markers; acute resistance exercise; resistance training
Low-grade inflammation and oxidative stress underlie chronic osteoarthritis. Although best-practice guidelines for osteoarthritis emphasize self-management including weight control and exercise, the role of lifestyle behavior change to address chronic low-grade inflammation has not been a focus of first-line management. This paper synthesizes the literature that supports the idea in which the Western diet and inactivity are proinflammatory, whereas a plant-based diet and activity are anti-inflammatory, and that low-grade inflammation and oxidative stress underlying osteoarthritis often coexist with lifestyle-related risk factors and conditions. We provide evidence-informed recommendations on how lifestyle behavior change can be integrated into “first-line” osteoarthritis management through teamwork and targeted evidence-based interventions. Healthy living can be exploited to reduce inflammation, oxidative stress, and related pain and disability and improve patients' overall health. This approach aligns with evidence-based best practice and holds the promise of eliminating or reducing chronic low-grade inflammation, attenuating disease progression, reducing weight, maximizing health by minimizing a patient's risk or manifestations of other lifestyle-related conditions hallmarked by chronic low-grade inflammation, and reducing the need for medications and surgery. This approach provides an informed cost effective basis for prevention, potential reversal, and management of signs and symptoms of chronic osteoarthritis and has implications for research paradigms in osteoarthritis.
Decreased exercise capacity negatively affects the individuals’ ability to adequately perform activities required for normal daily life and, therefore, the independence and quality of life. Regular exercise training is associated with improved quality of life and survival in healthy individuals and in cardiovascular disease patients. Also in patients with stable heart failure, exercise training can relieve symptoms, improve exercise capacity and reduce disability, hospitalisation and probably mortality. Physical inactivity can thus be considered a major cardiovascular risk factor, and current treatment guidelines recommend exercise training in patients with heart failure in NYHA functional classes II and III. Exercise training is associated with numerous pulmonary, cardiovascular, and skeletal muscle metabolic adaptations that are beneficial to patients with heart failure. This review discusses current knowledge of mechanisms by which exercise training is beneficial in these patients.
Heart failure; Exercise training; Exercise capacity; Quality of life; Neurohumoral effects; Endothelial effects; Anti-inflammatory effects
Interstitial lung disease encompasses a diverse group of chronic lung conditions characterised by distressing dyspnoea, fatigue, reduced exercise tolerance and poor health-related quality of life. Exercise training is one of the few treatments to induce positive changes in exercise tolerance and symptoms, however there is marked variability in response. The aetiology and severity of interstitial lung disease may influence the response to treatment. The aims of this project are to establish the impact of exercise training across the range of disease severity and to identify whether there is an optimal time for patients with interstitial lung disease to receive exercise training.
One hundred and sixteen participants with interstitial lung disease recruited from three tertiary institutions will be randomised to either an exercise training group (supervised exercise training twice weekly for eight weeks) or a usual care group (weekly telephone support). The 6-minute walk distance, peripheral muscle strength, health-related quality of life, dyspnoea, anxiety and depression will be measured by a blinded assessor at baseline, immediately following the intervention and at six months following the intervention. The primary outcome will be change in 6-minute walk distance following the intervention, with planned subgroup analyses for participants with idiopathic pulmonary fibrosis, dust-related interstitial lung disease and connective-tissue related interstitial lung disease. The effects of disease severity on outcomes will be evaluated using important markers of disease severity and survival, such as forced vital capacity, carbon monoxide transfer factor and pulmonary hypertension.
This trial will provide certainty regarding the role of exercise training in interstitial lung disease and will identify at what time point within the disease process this treatment is most effective. The results from this study will inform and optimise the clinical management of people with interstitial lung disease.
Australian New Zealand Clinical Trials Registry ACTRN12611000416998
Interstitial lung diseases; Diffuse parenchymal lung diseases; Idiopathic pulmonary fibrosis; Idiopathic interstitial pneumonias; Asbestosis; Sarcoidosis; Hypersensitivity pneumonitis; Connective tissue diseases; Exercise; Rehabilitation
Exercise training has been shown to reduce angina and promote collateral vessel development in patients with coronary artery disease. However, the mechanism whereby exercise exerts these beneficial effects is unclear. There has been increasing interest in the use of whole genome peripheral blood gene expression in a wide range of conditions to attempt to identify both novel mechanisms of disease and transcriptional biomarkers. This protocol describes a study in which we will assess the effect of a structured exercise programme on peripheral blood gene expression in patients with stable angina, and correlate this with changes in angina level, anxiety, depression, and exercise capacity.
Sixty patients with stable angina will be recruited and randomised 1:1 to exercise training or conventional care. Patients randomised to exercise training will attend an exercise physiology laboratory up to three times weekly for supervised aerobic interval training sessions of one hour in total duration. Patients will undergo assessments of angina, anxiety, depression, and peripheral blood gene expression at baseline, after six and twelve weeks of training, and twelve weeks after formal exercise training ceases.
This study will provide comprehensive data on the effect of exercise training on peripheral blood gene expression in patients with angina. By correlating this with improvement in angina status we will identify candidate peripheral blood transcriptional markers predictive of improvements in angina level in response to exercise training.
Clinicaltrials.gov identifier: NCT01147952
Patients with chronic kidney disease frequently present with chronic elevations in markers of inflammation, a condition that appears to be exacerbated by disease progression and onset of haemodialysis. Systemic inflammation is interlinked with malnutrition and muscle protein wasting and is implicated in a number of morbidities including cardiovascular disease: the most common cause of mortality in this population. Research in the general population and other chronic disease cohorts suggests that an increase in habitual activity levels over a prolonged period may help redress basal increases in systemic inflammation. Furthermore, those populations with the highest baseline levels of systemic inflammation appear to have the greatest improvements from training. On the whole, the activity levels of the chronic kidney disease population reflect a sedentary lifestyle, indicating the potential for increasing physical activity and observing health benefits. This review explores the current literature investigating exercise and inflammatory factors in the chronic kidney disease population and then attempts to explain the contradictory findings and suggests where future research is required.
Metabolic syndrome (MS) is a metabolic disorder associated with obesity, type-II diabetes, and "low grade inflammation", with the concomitant increased risk of cardiovascular events. Removal of the inflammatory mediator signals is a promising strategy to protect against insulin resistance, obesity, and other problems associated with MS such as cardiovascular disease. The aim of the present investigation was to determine the "inflammatory and stress status" in an experimental model of MS, and to evaluate the effect of a program of habitual exercise and the resulting training-induced adaptation to the effects of a single bout of acute exercise.
Obese Zucker rats (fa/fa) were used as the experimental model of MS, and lean Zucker rats (Fa/fa) were used for reference values. The habitual exercise (performed by the obese rats) consisted of treadmill running: 5 days/week for 14 weeks, at 35 cm/s for 35 min in the last month. The acute exercise consisted of a single session of 25-35 min at 35 cm/s. Circulating concentrations of IL-6 (a cytokine that regulates the inflammatory and metabolic responses), CRP (a systemic inflammatory marker), and corticosterone (CTC) (the main glucocorticoid in rats) were determined by ELISA, and that of noradrenaline (NA) was determined by HPLC. Glucose was determined by standard methods.
The genetically obese animals showed higher circulating levels of glucose, IL-6, PCR, and NA compared with the control lean animals. The habitual exercise program increased the concentration of IL-6, PCR, NA, and glucose, but decreased that of CTC. Acute exercise increased IL-6, CRP, and NA in the sedentary obese animals, but not in the trained obese animals. CTC was increased after the acute exercise in the trained animals only.
Animals with MS present a dysregulation in the feedback mechanism between IL-6 and NA which can contribute to the systemic low-grade inflammation and/or hyperglycaemia of MS. An inappropriate exercise intensity can worsen this dysregulation, contributing to the metabolic, inflammatory, and stress disorders associated with MS. Habitual exercise (i.e., training) induces a positive adaptation in the response to acute exercise.
Inflammatory bowel diseases are associated with increased adiponectin (APN) levels, which may exert pro-inflammatory effects in these individuals. Since habitual exercise may increase APN, the aim of this study was to determine how exercise training affects mice with acute colitis.
Male adiponectin knock out (APNKO) and wild type (WT) mice (C57BL/6) were randomly assigned to 4 different groups: 1) Sedentary (SED); 2) Exercise trained (ET); 3) Sedentary with dextran sodium sulfate (DSS) treatment (SED + DSS); and 4) Exercise trained with DSS (ET + DSS). Exercise-trained mice ran at 18 m/min for 60 min, 5d/wk for 4 weeks. Subsequently, the ET + DSS and the SED + DSS mice received 2% DSS in their drinking water for 5 days (d), followed by 5d of regular water.
The clinical symptoms of acute colitis (diarrhea, stool haemoccult, and weight loss) were unaffected by exercise and there was no difference between the APNKO and WT mice (p > 0.05) except on day 39. However, the clinical symptoms of the DSS-treated APNKO mice were worse than WT mice treated with DSS and had increased susceptibility to intestinal inflammation due to increased local STAT3 activation, higher IL-6, TNF-α, IL-1β and IL-10 levels, and as a result had increased intestinal epithelial cell proliferation (p < 0.05). Exercise training significantly decreased pro-inflammatory cytokines including IL-6, TNF-α and IL-1β (p < 0.05) in the DSS + EX APNKO mice but had no effect on epithelial cell proliferation. Exercise was also found to significantly decrease the phosphorylation expression of STAT3 in both WT and APNKO mice in DSS + EX group when compared to DSS + SED.
Exercise training may contribute in alleviating the symptoms of acute colitis and APN deficiency may exacerbate the intestinal inflammation in DSS-induced colitis.
Adipokines; Cytokines; Inflammation; Epithelial cell proliferation; Intestine