Exercise and Inflammation

Study Overview
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Brief Summary
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The purpose of this study is to test the hypothesis that aerobic exercise leads to attenuation of the inflammatory response to lipopolysaccharide (LPS) stimulation.

Detailed Description
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Aerobic exercise - the most widely recommended health behavior - is recognized to reduce the risk of coronary heart disease, so much so that consensus panels routinely include it as part of a cardioprotective regimen for healthy people, but the physiological or mechanistic basis of this protection is uncertain. Understanding the mechanisms has considerable public health significance because it will allow development and testing of targeted interventions to produce comparable cardioprotective effects more directly or in cases where aerobic exercise is not possible. This application proposes to test the hypothesis that aerobic training leads to attenuation of the inflammatory response to LPS stimulation and to examine the role played by exercise-induced increases in vagal activity, improvements in mood, and decreased expression of Toll Receptor 4 (TLR4), the cognate receptor for endotoxin expressed by monocytes.

Official Title
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Exercise and Inflammation: Autonomic, Affective & Cellular Mechanisms

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Behavioral: aerobic training
* Behavioral: Wait list


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 20-45 years old English-speaking Ambulatory BMI < 32 Pre-menopausal (women only) with regular cycle lengths between 26-32 days Average fitness as determined by American Heart Association standards (VO2max < 43 ml/kg/min for men, < 37 ml/kg/min for women) VO2max test Exclusion Criteria: Use of anti-psychotic medications Current of past major depressive disorder, or total symptom score > 10 BMI<18 Heart disease Hypertension Diabetes mellitus Neurologic disease Smoking Individuals with ischemic heart disease, cardiac arrhythmias, peripheral vascular disease, orthopedic problems such as foot, leg, hip and spine problems,movement disorders, other neurological disorders affecting gait or balance, conditions or treatments associated with impaired thermoregulation, or other medical problems, for which aerobic training would be contraindicated. Use of any medication with autonomic effects Use of birth control medication Ischemic changes, abnormal blood pressure responses, significant ectopy Appears to be at high risk to be unable to adhere to study protocol

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: aerobic training<br>12 weeks of aerobic training, 4 times/week | Behavioral: aerobic training<br>* 12 weeks of aerobic training, 4 times/week<br>* Other names: Training, aerobic;|
| Placebo Comparator: wait list control<br>wait list control condition, 12 weeks + 4 to parallel the deconditioning protocol in active intervention group | Behavioral: Wait list<br>* wait list control condition<br>* Other names: Condition, wait list control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tumor necrosis factor (TNF-alpha) | TNF-alpha will be measured from whole blood samples stimulated with lipopolysaccharide | change from before (pre) to after (post) 12 weeks of training & after 4 weeks of post-deconditioning | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mood, including depressive symptomatology and negative affect |  | change from before (pre) to after (post) 12 weeks of training & after 4 weeks of post-deconditioning | 
| interleukin 1 (IL-1), IL-6, IL-8, IL-10 | these cytokines will be measured from whole blood samples stimulated with lipopolysaccharide | change from before (pre) to after (post) 12 weeks of training & after 4 weeks of post-deconditioning | 
| TLR-4 | TLR-4 will be measured from blood samples | change from before (pre) to after (post) 12 weeks of training & after 4 weeks of post-deconditioning | 
| cerebral blood volume (CBV) in the dentate gyrus |  | change from before (pre) to after (post) 12 weeks of training |