Cytokine responses to acute and chronic exercise in multiple sclerosis.

Regular exercise reduces functional loss associated with multiple sclerosis (MS). However, the impact of exercise on inflammatory mediators associated with disease activity remains relatively unexplored. The purpose of this study was to determine whether ambulatory MS subjects would respond similarly to aerobic cycle training compared with matched controls on circulating immune variables, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. Eleven MS and 11 non-MS control subjects (8 women and 3 men in both groups) matched in age, height, body mass, body fat, and peak O(2) uptake completed the study. Subjects completed 30 min of cycle ergometry at 60% of peak O(2) uptake, 3 day/wk for 8 wk. Plasma cytokine concentrations were determined before and after exercise at weeks 0, 4, and 8. MS and control subjects showed a similar cytokine responses to exercise. IL-6 at rest tended to decrease (P = 0.08) with training in both groups. Resting plasma TNF-alpha tended to be higher in MS compared with controls throughout the study (P = 0.08). MS subjects showed elevated resting TNF-alpha in MS at the end of the 8-wk program (P = 0.04), whereas resting TNF-alpha remained unchanged in controls (P > 0.05). Resting plasma IFN-gamma at rest was elevated in MS subjects (P = 0.008) and unchanged in controls at the end of the intervention (P > 0.05). The response of plasma IL-6, TNF-alpha, and IFN-gamma after a single bout of exercise was similar between MS and control subjects (P > 0.05). Additional research to understand the impact of exercise on immune variables in MS is warranted.

Exercise and brain health--implications for multiple sclerosis: Part II--immune factors and stress hormones.

Part I of this review addressed the possible modulatory role of exercise on neuronal growth factors to promote brain health in neurodegenerative diseases such as multiple sclerosis (MS), which is characterized by varied patterns of inflammation, demyelination and axonal loss. Part II presents evidence that supports the potential neuroprotective effect of exercise on the modulation of immune factors and stress hormones in MS. Many current therapies used to attenuate MS progression are mediated, at least in part, through alterations in the relative concentrations of pro- and anti-inflammatory cytokines. Exercise-induced alterations in local and systemic cytokine production may also benefit immune function in health and disease. Exercise immunomodulation appears to be mediated by a complex interaction of hormones, cytokines and neural factors that may favorably influence immune variables in MS. The promising interplay between exercise and brain health in MS deserves further investigation.

Exercise and brain health--implications for multiple sclerosis: Part 1--neuronal growth factors.

The benefits of regular exercise to promote general health and reduce the risk of hypokinetic diseases associated with sedentary lifestyles are well recognized. Recent studies suggest that exercise may enhance neurobiological processes that promote brain health in aging and disease. A current frontier in the neurodegenerative disorder multiple sclerosis (MS) concerns the role of physical activity for promoting brain health through protective, regenerative and adaptive neural processes. Research on neuromodulation, raises the possibility that regular physical activity may mediate favourable changes in disease factors and symptoms associated with MS, in part through changes in neuroactive proteins. Insulin-like growth factor-I appears to act as a neuroprotective agent and studies indicate that exercise could promote this factor in MS. Neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor likely play roles in neuronal survival and activity-dependent plasticity. Physical activity has also been shown to up-regulate hippocampal BDNF, which may play a role in mood states, learning and memory to lessen the decline in cognitive function associated with MS. In addition, exercise may promote anti-oxidant defences and neurotrophic support that could attenuate CNS vulnerability to neuronal degeneration. Exercise exposure (preconditioning) may serve as a mechanism to enhance stress resistance and thereby may support neuronal survival under heightened stress conditions. Considering that axonal loss and cerebral atrophy occur early in the disease, exercise prescription in the acute stage could promote neuroprotection, neuroregeneration and neuroplasticity and reduce long-term disability. This review concludes with a proposed conceptual model to connect these promising links between exercise and brain health.

Cytokine responses to resistance training in people with multiple sclerosis.

Exercise for individuals with multiple sclerosis (MS) has been shown to improve cardiovascular function, increase strength and endurance, and reduce fatigue. The impact of exercise on immune function in the disease, however, remains mostly unexplored. Ten female MS patients participated in an 8 week programme of twice-weekly progressive resistance training, with pre- and post-training assessment of serum concentrations of cytokines IL-2, IL-4, IL-6, IL-10, CRP, TNF-alpha and IFN-gamma. After training, IL-4, IL-10, CRP and IFN-gamma showed statistically reduced resting concentrations in blood, while TNF-alpha showed non-significant reductions and IL-2 and IL-6 remained unchanged. These results suggest that progressive resistance training may have an impact on cytokine concentrations in individuals with MS and should be confirmed in studies with stronger statistical power. The impact of these changes on overall immune function in MS and on disease status and prognosis remains to be determined.

Cardiovascular/non-insulin-dependent diabetes mellitus risk factors and intramyocellular lipid in healthy subjects: a sex comparison.

Little is known about the relationship between intramyocellular lipid (IMCL) and coronary artery disease (CAD)/non-insulin-dependent diabetes mellitus risk factors. The aim of the study was to examine the relationship between IMCL and CAD/non-insulin-dependent diabetes mellitus risk factors in healthy male (n = 9) and female (n = 10) subjects with similar norm-based aerobic fitness and body composition. Nineteen volunteers (21-36 years) completed health and physical activity questionnaires, cardiovascular and body composition evaluation, and assessment of thigh IMCL using proton magnetic resonance spectroscopy. Outcome measures were blood pressure, total cholesterol, high-density lipoprotein cholesterol, C-reactive protein, interleukin 6, tumor necrosis factor alpha (TNF-alpha), homocysteine, insulin resistance (IR), percentage of body fat, waist-to-hip ratio, physical activity levels, and cardiovascular fitness. Analysis of variance was used for group comparisons. Correlation analyses were used to determine association between variables, and stepwise regression was used to determine predictive variables of IR. Women had 2-fold higher IMCL and greater IR than men (P < .05). Men had greater plasma homocysteine and interleukin 6 concentration (P < .05) as well as stronger correlations with CAD risk factors than female subjects. Correlation analyses using all subjects revealed a significant relationship between IMCL and waist-to-hip ratio, body weight, percentage of body fat, and IR. In the regression analysis, age, IMCL, and TNF-alpha were the strongest predictors of IR (R2 = 0.62, P < .01). Our results suggest that female subjects, matched for age and fitness, have higher IMCL compared with their male counterparts. IMCL was correlated with several CAD and prediabetes markers in both male and female subjects. In the final regression model, age, IMCL, and TNF-alpha were the strongest predictors of IR. Future studies with larger sample sizes are warranted.

Resistance training improves gait kinematics in persons with multiple sclerosis.

OBJECTIVE: To evaluate the effects of an 8-week lower-body resistance-training program on walking mechanics in persons with multiple sclerosis (MS). DESIGN: Repeated-measures design, evaluating gait kinematics before and after an 8-week progressive resistance-training intervention. SETTING: Biomechanics laboratory and fitness center (with conventional, commercially available resistance-training equipment). PARTICIPANTS: Eight ambulatory subjects with MS (age, 46.0+/-11.5 y) with Expanded Disability Status Scale scores ranging from 2.5 to 5.5. INTERVENTION: An 8-week progressive resistance-training program. MAIN OUTCOME MEASURES: Kinematic gait parameters including knee range of motion, duration of stance, swing, and double-support phases in seconds and as percentages of the stride time, percentage of stride time spent in stance, swing, and double-support phases, step length, foot angle, stride length, velocity, step width, and toe clearance for both the more affected and less affected lower limbs. Isometric strength, 3-minute stepping, fatigue, and self-reported disability were also measured. RESULTS: After 2 months of resistance training, there were significant increases (P<.05) in percentage of stride time in the swing phase, step length, stride length, and foot angle; and significant decreases (P<.05) in percentage of stride time in the stance and double-support phases, duration of the double-support phase, and toe clearance. Isometric leg strength improved (P<.05) in 2 of the 4 muscle groups tested. Fatigue indices decreased (P=.04), whereas self-reported disability tended to decrease (P=.07) following the training program. Three-minute stepping increased by 8.7%. CONCLUSIONS: Resistance training may be an effective intervention strategy for improving walking and functional ability in moderately disabled persons with MS.

Blood flow response to a postural challenge in older men and women.

BACKGROUND: The purpose of this study was to measure blood flow in the carotid and femoral arteries, heart rate and blood pressure in response to postural challenge in older adults. A second purpose was to determine if older men and women have different cardiovascular responses to a postural challenge such as tilt. METHODS: Thirty-seven healthy elderly men and women participated in this study (69-82 years old). All subjects had similar physical activity levels. Postural challenge was induced by a 60 degrees tilt at the level of the waist. Continuous carotid blood flow and femoral blood flow was measured with Doppler ultrasound. RESULTS: Carotid blood flow was significantly reduced 17% in both men and women immediately after tilt (p < 0.001), and by 3.2% two minutes after tilt (p < 0.001). Femoral blood flow decreased 59.4% in men and 61% in women immediately after tilt (p < 0.001), and remained significantly decreased two minutes after tilt by 21% (p <0.001). Heart rate increased by 15% in men (p < 0.001), and 26% in women immediately after the tilt (p < 0.001). Heart rate returned to resting values within two minutes in both men and women. Response to tilt was not significantly related to self-report physical activity levels or to six-minute walk time. CONCLUSION: A postural challenge induced larger changes in the femoral artery compared to the carotid artery. There were no differences between men and women to a tilt table test except for differences in heart rate response. There was no difference in the blood flow responses to postural challenge with physical activity level or between healthy older men and women.