Exercise influences the impact of polychlorinated biphenyl exposure on immune function.

Polychlorinated biphenyls (PCBs) are environmental pollutants and endocrine disruptors, harmfully affecting reproductive, endocrine, neurological and immunological systems. This broad influence has implications for processes such as wound healing, which is modulated by the immunological response of the body. Conversely, while PCBs can be linked to diminished wound healing, outside of PCB pollution systems, exercise has been shown to accelerate wound healing. However, the potential for moderate intensity exercise to modulate or offset the harmful effects of a toxin like PCB are yet unknown. A key aim of the present study was to examine how PCB exposure at different doses (0, 100, 500, 1000 ppm i.p.) altered wound healing in exercised versus non-exercised subgroups of mice. We examined PCB effects on immune function in more depth by analyzing the concentrations of cytokines, interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) in these wounds inflicted by punch biopsy. Mice were euthanized at Day 3 or Day 5 after PCB injection (n = 3-6) and skin excised from the wound area was homogenized and analyzed for cytokine content. Results revealed that wound healing was not signficantly impacted by either PCB exposure or exercise, but there were patterns of delays in healing that depended on PCB dose. Changes in cytokines were also observed and depended on PCB dose and exercise experience. For example, IL-1ß concentrations in Day 5 mice without PCB administration were 33% less in exercised mice than mice not exercised. However, IL-1ß concentrations in Day 3 mice administered 100 ppm were 130% greater in exercised mice than not exercisedmice. Changes in the other measured cytokines varied with mainly depressions at lesser PCB doses and elevations at higher doses. Exercise had diverse effects on cytokine levels, but increased cytokine levels in the two greater doses. Explanations for these diverse effects include the use of young animals with more rapid wound healing rates less affected by toxin exposure, as well as PCB-mediated compensatory effects at specific doses which could actually enhance immune function. Future work should examine these interactions in more detail across a developmental time span. Understanding how manipulating the effects of exposure to environemntal contaminants using behavioral modification could be very useful in certain high risk populations or exposed individuals.

Metabolic demands of law enforcement personal protective equipment during exercise tasks.

Many occupations require the use of personal protective equipment (PPE) but the added metabolic demands are unknown for certain professions. The purpose of this study was to quantify metabolic and perceptual differences between activity with and without the PPE ensemble required for police officers. Twelve participants were asked to complete experimental and control exercise sessions consisting of three modes of exercise (walking, jogging and stepping). A significant main effect (p < 0.01) for gear was found for heart rate (beats per minute) and VO2 (L/min) between conditions. Dependent t-tests revealed significant differences for perceived effort, discomfort and session rating of perceived exertion between trials. Medium to large effect sizes for all variables with significant main effects between modes (p < 0.01, η2 = 0.51-0.96, 1-ß = 0.98-1.0, d = 0.42-2.7) were observed. These findings help to increase awareness of how PPE affects metabolic demands and perception of discomfort during exercise.

Relationship between systemic inflammation and delayed-type hypersensitivity response to Candida antigen in older adults.

Research has shown that aging is associated with increased systemic inflammation as well as a reduction in the strength of immune responses. However, little evidence exists linking the decrease in cell-mediated immunity in older adults with other health parameters. We sought to examine the relationship between cell-mediated immunity as measured in vivo by the delayed-type hypersensitivity (DTH) response to candida antigen and demographic and physiological variables in older (65-80 y.o.) adults. Candida antigen response was not related to gender or obesity, or to a number of other physiological variables including fitness and body composition. However, positive responders had significantly lower serum C-reactive protein levels (CRP, p<0.05) vs. non-responders. Furthermore, subjects with CRP<4.75 mg•L(-1) had greater odds of developing a positive response compared to those with CRP>4.75 mg•L(-1). Therefore, positive responses to candida antigen in older adults appears to be related to lower levels of systemic inflammation.

Exercise, inflammation, and innate immunity.

Exercise has beneficial effects on chronic disease, and the drive to understand the mechanisms of these benefits is strong. This article presents several compelling potential mechanisms for the anti-inflammatory effect of exercise, including reduced percentage of body fat and macrophage accumulation in adipose tissue, muscle-released interleukin-6 inhibition of tumor necrosis factor-a, and the cholinergic anti-inflammatory pathway.

Cardiovascular exercise training extends influenza vaccine seroprotection in sedentary older adults: the immune function intervention trial.

OBJECTIVES: To determine whether cardiovascular exercise training resulted in improved antibody responses to influenza vaccination in sedentary elderly people who exhibited poor vaccine responses. DESIGN: Single-site randomized parallel-arm 10-month controlled trial. SETTING: University of Illinois at Urbana-Champaign. PARTICIPANTS: One hundred forty-four sedentary, healthy older (69.9 +/- 0.4) adults. INTERVENTIONS: Moderate (60-70% maximal oxygen uptake) cardiovascular exercise was compared with flexibility and balance training. MEASUREMENTS: The primary outcome was influenza vaccine response, as measured according to hemagglutination inhibition (HI) anti-influenza antibody titer and seroprotective responses (HI titer > or =40). Secondary measures included cardiovascular fitness and body composition. RESULTS: Of the 160 participants enrolled, 144 (90%) completed the 10-month intervention with excellent compliance ( approximately 83%). Cardiovascular, but not flexibility, exercise intervention resulted in improvements in indices of cardiovascular fitness, including maximal oxygen uptake. Although not affecting peak (e.g., 3 and 6 weeks) postvaccine anti-influenza HI titers, cardiovascular exercise resulted in a significant increase in seroprotection 24 weeks after vaccination (30-100% dependent on vaccine variant), whereas flexibility training did not. CONCLUSION: Participants randomized to cardiovascular exercise experienced improvements in influenza seroprotection throughout the entire influenza season, whereas those in the balance and flexibility intervention did not. Although there were no differences in reported respiratory tract infections, the exercise group exhibited reduced overall illness severity and sleep disturbance. These data support the hypothesis that regular endurance exercise improves influenza vaccine responses.

Exercise accelerates cutaneous wound healing and decreases wound inflammation in aged mice.

The purpose of this study was to determine the effect of exercise on wound healing and inflammation in young (3 mo) and old (18 mo) female BALB/cByJ mice. Mice were assigned to either exercise or sedentary control (control) groups. The exercise group mice were run on a motorized treadmill at a moderate intensity 30 min/day for 8 days. All mice were given four full-thickness dermal wounds, and the rate of wound closure was assessed daily for 10 days. Four months later, the aged mice were rerandomized to treatment, wounded again in different locations, and wounds were harvested at 1, 3, or 5 days postwounding. Wound tissue was analyzed for IL-1beta, IL-6, keratinocyte chemoattractant (KC), monocyte chemoattractant protein-1 (MCP-1), and TNF-alpha protein. Myeloperoxidase (MPO) activity and F4/80 mRNA were assessed as an indirect measure of neutrophil and macrophage content, respectively. There was a trend (P = 0.10) for exercise to reduce wound size in young mice, and exercise significantly (P < 0.05) decreased wound size in old mice. TNF-alpha, KC, and MCP-1 were significantly (P < 0.05) lower in wounds from exercised old mice compared with control. No group differences were found for wound IL-1beta or IL-6, MPO activity, or F4/80 mRNA. Our data suggest that exercise accelerates the wound healing process in old mice. This improved healing response in the old mice may be the result of an exercise-induced anti-inflammatory response in the wound.

Higher antibody, but not cell-mediated, responses to vaccination in high physically fit elderly.

The purpose of this study was to examine whether cardiovascular fitness, independent of confounding factors, was associated with immune responsiveness to clinically relevant challenges in older adults (60-76 yr). Thirteen sedentary, low-fit (LF; maximal O(2) uptake = 21.1 +/- 1.1 ml.kg(-1).min(-1)) and 13 physically active, high-fit (HF; maximal O(2) uptake = 46.8 +/- 3.4 ml.kg(-1).min(-1)) older adults participated in this study. Dietary intake was assessed, and a battery of psychosocial tests was administered. In vivo antibody and ex vivo proliferative and cytokine responses to influenza (Fluzone) and tetanus toxoid (TT) vaccination and delayed-type hypersensitivity skin tests were performed. HF elderly individuals displayed a higher antibody response to two of the three strains included in the Fluzone vaccine as measured by hemagluttination inhibition, but there was no difference between groups in influenza-specific ex vivo proliferation or IFN-gamma or IL-10 production. HF elderly individuals exhibited a lower IgG(1) response and a tendency for a higher IgG(2) response to the TT vaccine. There were, however, no differences in TT-specific ex vivo proliferation or IFN-gamma or IL-10 production. In contrast, HF subjects had higher proliferative responses to phytohemagluttinin. In addition, there were no differences in delayed-type hypersensitivity responses to fungal antigens between groups. These results suggest that, after accounting for confounding factors, HF elderly individuals have higher antibody responses to Fluzone vaccine and a Th2 skewing of the antibody response to TT. There was little evidence that HF mounted better cell-mediated immune responses to the Fluzone or TT vaccine measured in peripheral blood cells or to other recall antigens in vivo.

Exercise, inflammation, and innate immunity.

Regular exercise is protective against several chronic diseases ranging from physiologic diseases such as cardiovascular disease to neurologic diseases such as dementia and depression. Exciting recent research points to chronic inflammation as an underlying contributor to many age-related chronic diseases. Cross-sectional and longitudinal studies in animals and humans have shown both an acute and a chronic anti-inflammatory effect. Because innate immunity is a key regulator of inflammatory processes, and chronic inflammation contributes to many illnesses, the effect of regular exercise on innate immunity, most importantly macrophages, holds much promise in terms of defining these mechanisms. Unfortunately, the mechanisms responsible for the observed anti-inflammatory effect of regular exercise have not been elucidated. This article presents several compelling potential mechanisms for the anti-inflammatory effect of exercise, including loss of body fat, reductions in macrophage accumulation in adipose tissue, altered macrophage phenotype in adipose tissue, exercise-induced muscle production of IL-6, or alterations in the balance between the sympathetic and parasympathetic nervous systems. Further investigation to confirm or reject these testable hypotheses will allow better application of exercise therapy to treat and prevent illnesses associated with chronic inflammation.

Can exercise training improve immune function in the aged?

Many strategies have been used to improve immune function in the aged. Unfortunately, many of these interventions have been disappointing, impractical, costly to develop and administer, or accompanied by adverse side effects. Aside from dietary manipulation (caloric restriction without malnutrition or antioxidant supplementation), research involving behavioral preventative or restorative therapies has been lacking. Moderate exercise training has been shown to elicit beneficial outcomes in both the prevention and rehabilitation of many diseases of the elderly. It has been hypothesized that moderate levels of exercise improves, whereas strenuous exercise or overtraining suppresses, various immune function measures. Three general approaches have been implemented to study the impact of exercise on immune functioning in the elderly: (1) cross-sectional studies, (2) longitudinal studies, and (3) animal studies. In general, cross-sectional studies examining highly active elderly have demonstrated improved in vitro T cell responses to polyclonal stimulation when compared to sedentary elderly. This is corroborated by several animal studies that have shown improved splenic T cell responses in vitro. Unfortunately, human prospective studies have failed to demonstrate consistent improvements in various measures of immune function in older adults. However, it should be cautioned that these studies have included small samples followed over a short duration, measuring a limited number of in vitro immune parameters, with some failing to account for potential confounding influences. Although such findings have the potential to be of substantial public health importance, very few systematic studies have been conducted.