high-intensity interval training and regulatory t cells

Conditions: End Stage Renal Disease

Summary: regulatory t cells (tregs) are a small population of t cells compromising of 1% to 5% of the total t cells in the body but they are playing a fundamental role in the maintenance of the immune homeostasis. these cells modulate the immune system by suppressing the effector activity and thus preventing autoimmune diseases and chronic inflammatory processes. treg cell numbers have shown to increase with physical activity, and this increment has been directly correlated with exercise intensity. these results suggest that the increased treg frequency may contribute to the beneficial effects of exercise on disorders associated with autoimmune disease or chronic low-grade inflammation such as atherosclerosis, diabetes mellitus, chronic kidney disease or cancer. the overall purpose of this study is to determine the influence high-intensity interval training (hiit) on the frequency and quality of peripheral treg cells.

tregs have been studied in clinical practice for different therapeutic applications. in the past several years there has been a significant interest in the transplant community to develop tolerance in order to substantially decrease or even eliminate the need of immuno-suppressive regimens. a growing body of evidence recognizes the balance between graft-reactive effector cells and graft-protective suppressor treg cells as the ultimate determinant of long-term allograft survival. as a result, there is a major interest in transplantation to enhance the suppressor immune response as an alternative or complementary approach to reach a clinical tolerogenic state and preserve graft function. exercise improves baseline immune function and helps to maintain immune homeostasis. treg cell numbers have shown to increase with physical activity, and this increment has been directly correlated with exercise intensity. these results suggest that the increased treg frequency may contribute to the beneficial effects of exercise on disorders associated with autoimmune disease or chronic low-grade inflammation such as atherosclerosis, diabetes mellitus, chronic kidney disease or cancer. primary objectives: the overall purpose of this study is to determine the influence high-intensity interval training (hiit) on the frequency and quality of peripheral treg cells. secondary objectives: effects of hiit in other t cell populations. effects of hiit in plasma concentration of inflammatory and metabolic markers. effects of hiit in obese vs lean. design: this is a prospective, single center, single-arm "pre-test/post-test" study designed to evaluate the safety, feasibility and initial efficacy of a 12-week hiit regimen to increase the frequency and quality of peripheral treg cells. all participants will have a pre-test (baseline) evaluation followed by a treatment and then a post-test.

Eligibility criteria:
inclusion criteria: * age between 18 and 65 years old. * bmi between 18.5 and 25 or above 30. rationale: we want to include "obesity" as categorical covariate in the influence of hiit and discriminate the participants between "lean" (bmi range 18.5-25) and "obese" (bmi \> 30) * sedentary lifestyle (fewer than 5,000 steps per day) * fluent in english, able to understand and provide informed consent. * subjects willing to participate in the study and comply with study requirements as evidenced by signed institutional review board (irb)-approved informed consent. exclusion criteria: * age under 18 or over 65 * bmi under 18.5 or between 25 and 30. * active lifestyle (more than 5,000 steps per day). * previous chronic use of systemic glucocorticoids, immune-suppressors or immuno-modulators in the preceding 3 months. * patients with significant or active infection: hiv negative by elisa or reverse transcription polymerase chain reaction (rt-pcr) \[if elisa is positive and rt-pcr is negative, the elisa is considered false positive\]; negative serology for hepatitis b and c. * active malignancy or history of malignancy within 1 year. * be pregnant or breastfeeding. * hemoglobin less than 9.0 g/dl at the time of blood drawing. * platelet count less than 100,000/\* at the time of blood drawing. * white blood count less than 4 and/or absolute neutrophil count less than 1500/\* at the time of blood drawing. * participation in any other study that involved investigational drug or regimens in the preceding 12 months. * history of delayed or abnormal wound healing. * any immuno-related condition, chronic illness or prior treatment which, in the opinion of the investigator, precludes study participation. * inability or unwillingness of participant to comply with study protocol or procedures. * impaired consent capacity. * any chronic use of anticoagulation. * recipient of blood transfusion in 3 months prior to blood drawing. * any orthopedic condition or chronic pain that prevents them from cycling. * any symptomatic coronary artery disease prior enrollment within 3 months or any intervention for it in the past 6 months. * any symptomatic current heart failure (new york heart association class iii and iv), significant valvar heart disease. * history of non-compliance. * the study will not include any vulnerable population such as fetuses, pregnant women, children, or prisoners.

Keywords: high intensity interval training exercise obesity inflammation treg