Abstract
Background: Cytokines are a group of low-molecular-weight regulatory proteins that produced by cells in response to stimulation. In fact, they are the response of immune system to exercise. Also, many cytokines such as IL-6 and TNFα are secreted from adipose tissue in obese people. So the aim of this study was to investigate, comparison the effect of one session submaximal exercise in plasma levels of IL6 and TNFα in obesity and non-obesity women.
Method: Sixteen healthy women ages 20-30 years old participated in the study. Subjects were classified into obese (n=8) and nonobese (n=8) group who performed submaximal exercise program (50-65% HRM) for 30min. Blood samples were taken for cytokines measurement, before and after exercise. Data were analyzed with SPSS15. For demonstrating the changes of variables after exercise t-test were used and covariance was applied for comparing two groups.
Result: A significant improvement was observed in IL-6 in two groups after 30 minutes submaximal exercise. But results showed levels of TNFα increased significantly in obese subjects but not for non-obese subjects. In comparing two groups, there were no significant changes in levels of IL-6 and TNFα after 30 minutes submaximal exercise.
Conclusion: After submaximal exercise, plasma level of IL6 and TNFα may increase and adipose tissue is a significant source of their circulating.
Introduction
Cytokines are a group of low-molecular-weight regulatory proteins in the body that secreted by leucocytes and a variety of other cells such as the vascular endothelium in response to a number of inducing stimulus.1-2
They are divided into several different families, which include the interleukins (IL), tumor necrosis factors (TNFs), interferon, growth factors, colony stimulating factors (CSFs), and cell adhesion molecules.
Each family of cytokines contributes to species aspects of acute inflammation. Cytokines may be further characterized as either Pro- or anti-inflammatory, based loosely on their predominant action. At the onset of inflammation there is an up-regulation of the pro inflammatory cytokines.2
Proinflammatory cytokines (signaling proteins of immune cells), such as TNFα and IL-6, have a pivotal role in coordinating the body's response to inflammation.3 TNFα effectively induces a local inflammatory response and helps to control infections.1 IL-6 causes lymphocyte activation and antibody production. IL-6 and TNFα, along with IL-1, synergistically control infection by regulating the production of acutephase proteins and by raising body temperature.1-4
It should be attention; another component of the immune system response to exercise is cytokines.5-6 Cytokines serve in a network to help regulate signaling of innate and specific immune responses. Traditionally, cytokine responses to exercise, in particular IL-6 and TNFα, have been interpreted as an immune mediated host defense.6 Plasma-IL-6 increases with exercise that is related to exercise intensity, duration, the mass of muscle recruited, and one's endurance capacity.1
Recent studies clearly demonstrated that muscle contractions without any muscle damage induce a marked elevation in plasma IL-6.1-2-3 Most studies have reported that exercise does not induce an increase in plasma levels of TNFα and it seems that exercise induces a very strong antiinflammatory cytokine response, with the appearance of IL-6 in the circulation being by far the most marked and its appearance preceding that of other cytokines.1
On the other hand, many cytokines are secreted from adipose tissue in obese people.1-7 There is much evidence that suggest cytokines can modulate metabolism and it should be attention, body adipose tissue may account for about 20-30% of IL-6 concentration during basal conditions that can be regulated by physical activity. In fact exercise may play an important role on adipose tissue.7-8-9-10-14
So, the aim of this study was to investigate, comparison the effect of one session submaximal exercise in plasma levels of IL6 and TNFα in obesity and non-obesity women which this proposal hasn't been investigated in former issues.
Method and material
This semi-experimental study conducted in Khorasgan Azad University. Sixteen healthy women ages 20-30 years old participated in the study. Subjects were classified into overweight (n=8) and normalweight (n=8) group. Overweight was defined as having 35 <body fat percent<45 and normalweight was 23<body fat percent<25.
Risk stratification
A risk stratification form about information of medical or family history of disease, height and weight and current medications was completed by all subjects following initial informed consent. It should be notice, that weight, WHR, BMI and body fat percent were identified with Body Composition Analyzer 3.0 (Biospace Company, Korea).
In addition, FBS, Total Serum Cholesterol, Low-density Lipoprotein, Cholesterol and High-density Lipoprotein were measured and all subjects were reported to be non-smoker.
Subjects arrived in the laboratory after an overnight fast to participate in the study. They were instructed to abstain from alcohol, caffeine and strenuous exercise for 24h prior to testing.
Blood samples were taken 15 minutes prior exercise program and immediately after it.
At the beginning, subjects rested on the chair and blood samples (preexercise) were drawn from antecubital vein. Then they began exercise program and heart rate were continuously monitored throughout the exercise.
Exercise program
Initially, subjects warm-up for ten minute by performing stretching, jogging and.... training. After that, they running on the treadmill with 50- 65% of maximal heart rate (age-220) for 20 min and then at the end of exercise program, subjects performed cool down by walking and stretching training for 10 min.
Cytokine measurement
For cytokines measurement (Interleukin-6 and TNFα), 5-ml blood was drawn into a glass tube and were centrifuged at the room temperature, separated and frozen at -70c and stored until subsequent analysis. IL-6 and TNFα were analyzed by commercially available enzyme linked immunosorbent assay (ELISA kits, Bender systems, Australia). At the end of the program all data were collected and analyzed with SPSS15 and the effects of exercise training were evaluated. For comparing the mean of variables outcome between two groups covariance was used.
Results
We studied Sixteen healthy women between 20-30 years old. At baseline mean and standard deviation of some physical and metabolic characteristics such as weight, fat percent, WHR and BMI of all subjects are described in table 1.
Table 2 illustrates the changes of variables in response to exercise in both groups with t-test.
A significant improvement was observed in IL-6 in two groups after 30 minutes submaximal exercise. On the other hand, results showed levels of TNFα increased significantly in obese subjects but not for non-obese subjects.
Also, in comparing two groups with covariance, there were no significant changes in levels of IL-6 and TNFα after 30 minutes sub maximal exercise which showed in table 3.
Discussion
This study provided information about increases of plasma concentration of IL6 in both obesity and normal groups after the 30 min submaximal exercise. These results are in agreement with several investigations. Brian W. Timmons et al. study demonstrated IL6 elevation in serum in young adult men after 60min strenuous exercise that showed, the level of increase in IL6 after exercise is typically dependant to intensity of exercise.6 Also peterson WA, suggested moderate exercise has major effects on muscle-derived IL-6 and it increases plasma-IL-6.1
In addition, Ludmila Cosio-Lima et al. expressed increases of IL6 in old non diabetic and young health groups after submaximal incremental treadmill test. It should be noted, release of plasma IL6 is related to exercise intensity, duration, the mass of skeletal muscle involved and endurance capacity of individual.11
Furthermore, Tongjinan You et al. considered that strenuous acute exercise often increases cytokine production (IL6 and TNFα) due to muscle tissue injury. 8-9
Moreover C.P Fisher et al. suggested obesity was associated with elevated magnitude of IL6 that is similar with our study.7 And peterson WA showed IL-6 stimulates lipolysis as well as fat oxidation.
Another factors which investigated in our study, were TNFα. In our data, TNFα significantly increased in obesity group but not in normal group during the study.
Brian et al. revealed that TNFα level didn't change after exercise in men which is agree with our results.6
This result maybe for the reason that TNFα generally increases only with high intensity, long duration exercise that engage a large muscle mass.
On the other hand, some studies indicated physiological concentrations of IL-6 inhibit the production of the proinflammatory cytokine TNFα.1
Another studies suggested that production of TNFα enhanced after exercise task that is likely to be related to an inflammatory response to exercise. 4-11 The physiological mechanism of IL6 and TNFα elevation in response to exercise has not been fully revealed. Several similarities exist between high intensity exercises and immune reactions inflammatory processes such as mobilization and action of leukocytes, induction of acute phase response, increases in proinflammatory cytokine production, cellular infiltration and tissue damage.4
The results indicated that in response to submaximal exercise, plasma IL6 increases from basal level, mainly due to a major release of contracting skeletal muscle. 4 On the other hand, exercise induced muscle injury has been attended to be primary stimulus for the IL6 response. Recent studies suggest that exercised muscle stimulates with complex intra muscular signaling and release IL6, independently of muscle damage. Subsequently, muscle damage per se induces a repair response, including macrophage entrance into the muscle, causing further IL6 production. This injury persuaded IL6 response is delayed and smaller than the IL6 production related to muscle contraction.8-12
On the other hand, obesity is associated with a number of metabolic complications including changes in the plasma lipid profile, such as increase in free fatty acids that increase in FFA can result in the activation of proinflammatory genes.8-14
It should be noted, under normal physiological conditions, proinflammatory cytokines induce lipolysis after acute aerobic exercise. As adipose tissue is a serious organ that produces and exudes proinflammatory cytokines and their soluble receptors and lipolysis occurs in adipose tissue. It is reasonable to consider that the loss of body fat with exercise could be one method considered that links changes in inflammation and lipolysis. 8-9-13
At the end we concluded that after submaximal exercise, plasma level of IL6 and TNFα may increase that could be in response to muscle injury after continuous contractions or adipose tissue. That adipose tissue is a significant source of circulating IL6 and TNFα and these cytokines and their receptors are highly revealed in individual with more fat.
Acknowledgment
We thank all staffs and anyone who help us in this study.
Conflict of Interests
Authors have no conflict of interests.
Refrence
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2. Smith LL, Anwar A, et al. Cytokines and cell adhesion molecules associated with high-intensity eccentric exercise. Eur J Appl Physiol. 2000; 82: 61-67.
3. Papanicolaou DA, Wilder RL, et al. The pathophysiologyic roles of interleukin-6 in human disease. Ann Intern Med. 1998; 128: 127-137.
4. Goebel UM, Mills JP, et al. Interleukin-6 and Tumor Necrosis Factor-α production after acute psychological stress, exercise and infused isopoterenol. Psychosomatic Medicine. 2000; 62: 591-598.
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6. Timmons WB, Tarnopolsky A.M, et al. Immune responses to strenous exercise and carbohydrate intake in boys and men. 2004; 56.
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8. You T, Berman MD et al. Effects of Hypocaloric Diet and Exercise Training on Inflammation and Adipocyte Lipolysis in Obese Postmenopausal Women. The Journal of Clinical Endocrinology & Metabolism. 2003; 89(4):1739-1746.
9. Nicklas JB , You T, Pahor M. Behavioral treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training. CMAJ. 2005; 172 (9).
10. Harris AR, Padilla J, et al. The flow-mediated dilation response to acute exercise in overweight active and inactive men. Integrative Physiology. 2008; 16: 578-584.
11. Cosio-Lima L, Schuler P, et al. Preliminary study of the effects of age and type2 diabetes on the release of IL-6, IL-10, TNFα and cortisol in response to acute exercise. Journal of exercise physiology.2008; 11.
12.Kasapis C, Thompson DP. The effect of physical activity on serum CRP and inflammatory makers: A systematic review. J AM Coll Cardiol. 2005; 45:1563-1569.
13. Gallistl S, Sudi KM, et al. Changes in serum interleukin-6 concentrations in obese children and adolescents during a weight reduction program. International Journal of Obesity. 2001; 25: 1640- 1643.
14. Meyer A, Kundt G, et al. Improvement of early vascular changes and cardiovascular risk factors in obese children after a six month exercise program. Journal of American College of Cardiology. 2006;48.
Farzaneh Taghian , PHD, Professor of Exercise Physiology, Islamic Azad University (Khorasgan Branch), Isfahan, Iran
Fatemeh esteki Ghashghaei , Former MSc student of Exercise Physiology, Islamic Azad University (Khorasgan Branch), Isfahan, Iran.
Rokhsareh Badami , PHD, Assistant Professor of Exercise Physiology, Islamic Azad University (Khorasgan Branch), Isfahan, Iran.
Samira Esteki Ghashghaei , MSc, Physical Education, Islamic Azad University (Babol Branch), Mazandaran, Iran.
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