Nicolette C. Bishop

The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease

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.

Respiratory infection risk in athletes: association with antigen-stimulated IL-10 production and salivary IgA secretion

The purpose of this study was to examine factors influencing susceptibility to upper respiratory tract infections (URTI) in 18–35‐year‐old men and women engaged in endurance‐based physical activity during the winter months. Eighty individuals (46 males, 34 females) provided resting blood and saliva samples for determination of markers of systemic immunity. Weekly training and illness logs were kept for the following 4 months. Thirty subjects did not experience an URTI episode and 24 subjects experienced 3 or more weeks of URTI symptoms. These illness‐prone subjects had higher training loads and had ∼2.5‐fold higher interleukin (IL)‐4 and IL‐10 production by antigen‐stimulated whole blood culture than the illness‐free subjects. Illness‐prone subjects also had significantly lower saliva S‐IgA secretion rate and higher plasma IgM (but not IgA or IgG) concentration than the illness‐free subjects. There were no differences in circulating numbers of leukocyte subtypes or lymphocyte subsets between the illness‐prone and illness‐free subjects. The production of IL‐10 was positively correlated and the S‐IgA secretion rate was negatively correlated with the number of weeks with infection symptoms. It is concluded that high IL‐10 production in response to antigen challenge and low S‐IgA secretion are risk factors for development of URTI in physically active individuals.

Modification of immune responses to exercise by carbohydrate, glutamine and anti-oxidant supplements

Immunosuppression in athletes involved in heavy training is undoubtedly multifactorial in origin. Training and competitive surroundings may increase the athletes exposure to pathogens and provide optimal conditions for pathogen transmission. Heavy prolonged exertion is associated with numerous hormonal and biochemical changes, many of which potentially have detrimental effects on immune function. Furthermore, improper nutrition can compound the negative influence of heavy exertion on immunocompetence. An athlete exercising in a carbohydrate‐depleted state experiences larger increases in circulating stress hormones and a greater perturbation of several immune function indices. The poor nutritional status of some athletes may predispose them to immunosuppression. For example, dietary deficiencies of protein and specific micronutrients have long been associated with immune dysfunction. Although it is impossible to counter the effects of all of the factors that contribute to exercise‐induced immunosuppression, it has been shown to be possible to minimize the effects of many factors. Athletes can help themselves by eating a well‐balanced diet that includes adequate protein and carbohydrate, sufficient to meet their energy requirements. This will ensure a more than adequate intake of trace elements without the need for special supplements. Consuming carbohydrate (but not glutamine or other amino acids) during exercise attenuates rises in stress hormones, such as cortisol, and appears to limit the degree of exercise‐induced immunosuppression, at least for non‐fatiguing bouts of exercise. Evidence that high doses of anti‐oxidant vitamins can prevent exercise‐induced immunosuppression is also lacking.

Physical Exercise in Patients with Severe Kidney Disease

Patients with advanced chronic kidney disease (CKD), especially those on long-term dialysis, often suffer from muscle wasting and excessive fatigue. It is known that inactivity, muscle wasting and reduced physical functioning are associated with increased mortality in CKD. Known causes include uraemic myopathy and neuropathy, inactivity, and anaemia. Exercise in patients receiving regular dialysis treatment for end-stage renal disease was first introduced 3 decades ago, but is still only offered in a minority of renal units around the world, despite a significant body of evidence to support its use. Work is needed to increase awareness of the potential benefits of increased physical activity for patients with advanced CKD. This review summarizes the mechanisms of exercise intolerance and debility in advanced CKD patients, the methods used for the estimation of functional capacity, the options currently available for exercise training, and their influence on the well-being of this group of patients.

Carbohydrate and fluid intake affect the saliva flow rate and IgA response to cycling.

PURPOSE The purpose of this study was to examine the effect of regular CHO beverage ingestion and restricted fluid intake on various salivary parameters during prolonged cycle exercise. METHODS In a randomized block design, 15 recreationally active men cycled for 2 h at 60% VO2max on three occasions, separated by 1 wk. On the CHO and placebo (PLA) treatments, subjects consumed either a glucose (60 g x L(-1)) or placebo drink before (400 mL), during (150 mL every 15 min), and after (400 mL) the exercise. On the restricted fluid intake (RFI) treatment subjects were given a total of 200 mL of placebo fluid to take as desired every 15-min during the exercise. Timed, unstimulated saliva samples were collected preexercise, at 1, 1.5, and 2 h of exercise and at 1 h postexercise. Blood samples were obtained from a subset of 8 subjects preexercise, postexercise, and at 1 h postexercise. RESULTS Postexercise plasma glucose levels were 18% and 20% lower on the PLA and RFI treatments, respectively, compared with the CHO treatment (P < 0.01). Saliva flow rates were significantly higher on the CHO treatment compared with the RFI treatment at 1.5 h and 2 h of exercise (P < 0.01 and P < 0.05, respectively). Salivary IgA (s-IgA) concentration was significantly lower on the CHO treatment compared with the RFI treatment throughout the exercise (P < 0.05). No other differences were seen between treatments for either saliva flow rate or s-IgA concentration. Neither s-IgA secretion rate, alpha-amylase activity, nor alpha-amylase secretion rate were affected by treatment. CONCLUSIONS These findings suggest that CHO and fluid intake influence the s-IgA and saliva flow rate response to prolonged submaximal exercise.

The effects of carbohydrate supplementation on immune responses to a soccer-specific exercise protocol.

The aim of this study was to determine the effect of carbohydrate (CHO) versus placebo (PLA) beverage consumption on the immune and plasma cortisol responses to a soccer-specific exercise protocol in 8 university team soccer players. In a randomized, counterbalanced design, the players received carbohydrate or placebo beverages before, during and after two 90 min soccer-specific exercise bouts (3 days apart) designed to mimic the activities performed and the distance covered in a typical soccer match. Blood and saliva samples were collected before, during and after the exercise protocol. Plasma lactate concentration increased to approximately 4 mmol x l(-1) at 45 and 90 min of exercise in both treatments (P<0.01). Plasma glucose concentration was significantly lower after 90 min of exercise with ingestion of the placebo than the carbohydrate (PLA: 4.57+/-0.12 mmol x l(-1); CHO: 5.49+/-0.11 mmol x l(-1); P<0.01). The pattern of change in plasma cortisol, circulating lymphocyte count and saliva immunoglobulin A secretion did not differ between the carbohydrate and placebo trials. Blood neutrophil counts were 14% higher 1 h after the placebo trial than the carbohydrate trial (PLA: 4.8+/-0.5x10(9) cells x l(-1); CHO: 4.2+/-0.5x10(9) cells x l(-1); P = 0.06), but the treatment had no effect on the degranulation response of blood neutrophils stimulated by bacterial lipopolysaccharide. We conclude that, although previous studies have shown that carbohydrate feeding is effective in attenuating immune responses to prolonged continuous strenuous exercise, the same cannot be said for a soccer-specific intermittent exercise protocol. When overall exercise intensity is moderate, and changes in plasma glucose, cortisol and immune variables are relatively small, it would appear that carbohydrate ingestion has only a minimal influence on the immune response to exercise.

Nutritional aspects of immunosuppression in athletes

The literature suggests that a heavy schedule of training and competition leads to immunosuppression in athletes, placing them at a greater risk of opportunistic infection. There are many factors which influence exercise-induced immunosuppression, and nutrition undoubtedly plays a critical role. Misinterpretation of published data and misleading media reports have lead many athletes to adopt an unbalanced dietary regimen in the belief that it holds the key to improved performance. Some sports have strict weight categories, whilst in others low body fat levels are considered to be necessary for optimal performance or seen as an aesthetic advantage. This leads some athletes to consume a diet extremely low in carbohydrate content which, whilst causing rapid weight loss, may have undesirable results which include placing the athlete at risk from several nutrient deficiencies. Complete avoidance of foods high in animal fat reduces the intake of protein and several fat-soluble vitamins. On the other hand, diets with a very high carbohydrate content are usually achieved at the expense of protein.In addition, anecdotal and media reports have often promoted the supposed performance benefits of certain vitamins and minerals, yet most athletes do not realise that micronutrient supplementation is only beneficial when correcting a deficiency, and to date there is little scientific evidence to substantiate claims that micronutrients act as an ergogenic aid. Moreover, excessive intakes of micronutrients can be toxic.Deficiencies or excesses of various dietary components can have a substantial impact on immune function and may further exacerbate the immunosuppression associated with heavy training loads. This review examines the role of nutrition in exercise-induced immunosuppression and the effect of both excessive and insufficient nutrient intake on immunocompetence. As much of the present literature concerning nutrition and immune function is based on studies with sedentary participants, the need for future research which directly investigates the relationship between exercise, training, immunity and nutrition is highlighted.

Nutritional strategies to counter stress to the immune system in athletes, with special reference to football

Abstract Although epidemiological data indicate that athletes are at increased risk of upper respiratory tract infection during periods of heavy training and the 1 – 2 week period following endurance race events, there is very limited information on the responses to football training and match-play. For several hours after heavy exertion, components of both the innate (e.g. natural killer cell activity and neutrophil oxidative burst activity) and adaptive (e.g. T and B cell function) immune system exhibit suppressed function. Although such responses to football training and competition do not appear to be as pronounced, variations in immune cell numbers and function are reported in professional footballers over the course of a season. Attempts have been made through nutritional means (e.g. glutamine, vitamins C and E, and carbohydrate supplementation) to attenuate immune changes following intensive exercise and thus lower the risk of upper respiratory tract infection. Carbohydrate supplementation during heavy exercise has emerged as a partial countermeasure and attenuates increases in blood neutrophil counts, stress hormones, and inflammatory cytokines, but has little effect on decrements in salivary IgA output or natural killer cell function. Animal research indicates that other nutritional components such as beta-glucan, quercetin, and curcumin warrant human investigations to determine if they are effective countermeasures to exercise-induced immune dysfunction.

Salivary IgA response to prolonged exercise in a cold environment in trained cyclists.

PURPOSE The purpose of the present study was to determine the effect of a prolonged bout of exercise in freezing cold conditions on saliva immunoglobulin A (s-IgA) responses in endurance-trained males. METHODS Using a randomized cross-over design, 15 trained male cyclists cycled for 2 h on a stationary ergometer at 70% VO(2max) in an environmental chamber on one occasion at a temperature of -6.4 +/- 0.1 degrees C (cold) and on another occasion at a temperature of 19.8 +/- 0.2 degrees C (control). Trials began at 12:30 h to avoid the fall in s-IgA concentration that occurs during the morning hours. Unstimulated whole-saliva samples were collected over a 2-min period at preexercise, postexercise, and 2-h postexercise. The s-IgA concentration was determined using a sandwich-type ELISA method. RESULTS Saliva flow rate decreased postexercise by 31%, returning to preexercise levels by the 2-h postexercise collection (main effect of time: < 0.01). The decrease in saliva flow rate postexercise in the control trial (39% compared with 22% on cold trial) approached significance (interaction: = 0.08) and may have accounted for the corresponding increase in s-IgA concentration postexercise in the control trial (s-IgA concentration: control preexercise; 91 +/- 12; postexercise; 110 +/- 13 mg x L(-1); < 0.05). Saliva IgA secretion rate decreased postexercise by 19.5% returning to preexercise levels by 2-h postexercise measure (main effect of time: < 0.05). CONCLUSIONS These data show that performing a bout of prolonged exercise results in a reduction in s-IgA secretion rate. Additionally, these data demonstrate that performing prolonged exercise in freezing cold conditions does not influence saliva flow rate or s-IgA secretion rate responses to prolonged exercise.

Evidence for Anti-Inflammatory Effects of Exercise in CKD

CKD is associated with a complex state of immune dysfunction characterized by immune depression, predisposing patients to infections, and immune activation, resulting in inflammation that associates with higher risk of cardiovascular disease. Physical exercise may enhance immune function and exert anti-inflammatory effects, but such effects are unclear in CKD. We investigated the separate effects of acute and regular moderate-intensity aerobic exercise on neutrophil degranulation (elastase release), activation of T lymphocytes (CD69 expression) and monocytes (CD86 and HLA-DR expression), and plasma inflammatory markers (IL-6, IL-10, soluble TNF-receptors, and C-reactive protein) in patients with predialysis CKD. A single 30-minute (acute) bout of walking induced a normal pattern of leukocyte mobilization and had no effect on T-lymphocyte and monocyte activation but improved neutrophil responsiveness to a bacterial challenge in the postexercise period. Furthermore, acute exercise induced a systemic anti-inflammatory environment, evidenced by a marked increase in plasma IL-10 levels (peaked at 1 hour postexercise), that was most likely mediated by increased plasma IL-6 levels (peaked immediately postexercise). Six months of regular walking exercise (30 min/d for 5 times/wk) exerted anti-inflammatory effects (reduction in the ratio of plasma IL-6 to IL-10 levels) and a downregulation of T-lymphocyte and monocyte activation, but it had no effect on circulating immune cell numbers or neutrophil degranulation responses. Renal function, proteinuria, and BP were also unaffected. These findings provide compelling evidence that walking exercise is safe with regard to immune and inflammatory responses and has the potential to be an effective anti-inflammatory therapy in predialysis CKD.