The effect of exercise on plasma soluble IL-6 receptor concentration: a dichotomous response (original) (raw)
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European Journal of Sport Science Interleukin-6: Possible biological roles during exercise
Interleukin-6 (IL-6) is a multifunctional cytokine that exerts its modulatory effects on cells that express membrane bound IL-6 receptors; however, IL-6 in a complex with soluble IL-6R can bind to any cell that express glycoprotein 130 (gp130). Thus, all cell types may respond to the pro-as well as anti-inflammatory properties of IL-6. Since the first report of acute exercise-induced increase in plasma IL-6 in the early 1990s, scientists have tried to elucidate the factors that influence the magnitude of change of plasma IL-6, as well as the possible biological roles of this cytokine. Evidence suggests that exercise intensity and duration as well as the form of contraction (e.g. eccentric or concentric) and muscle damage all influence IL-6 response to acute exercise. However, data on training status and performance on plasma IL-6 concentration changes during exercise are more inconclusive, as discussed in this review. In the last decade, most of the studies have focused on IL-6 as an 'energy sensor' possibly secreted by skeletal muscle that activates glycogenolysis in the liver and lipolysis in fat tissue in order to provide muscle with the growing energy demands during exercise.
Interleukin-6 in acute exercise and training: what is the biological relevance?
Exercise immunology review, 2006
It is now recognized that contracting skeletal muscle may synthesize and release interleukin-6 (IL-6) into the interstitium as well as into the systemic circulation in response to a bout of exercise. Although several sources of IL-6 have been demonstrated, contracting muscles contributes to most of the IL-6 present in the circulation in response to exercise. The magnitude of the exercise-induced IL-6 response is dependent on intensity and especially duration of the exercise, while the mode of exercise has little effect. Several mechanisms may link muscle contractions to IL-6 synthesis: Changes in calcium homeostasis, impaired glucose availability, and increased formation of reactive oxygen species (ROS) are all capable of activating transcription factors known to regulate IL-6 synthesis. Via its effects on liver, adipose tissue, hypothalamic-pituitary-adrenal (HPA) axis and leukocytes, IL-6 may modulate the immunological and metabolic response to exercise. However, prolonged exercis...
Immunohistochemical detection of interleukin-6 in human skeletal muscle fibers following exercise
The FASEB Journal, 2003
Interleukin-6 (IL-6) is produced by many different cell types. Human skeletal muscles produce and release high amounts of IL-6 during exercise; however, the cell source of origin in the muscle is not known. Therefore, we studied the protein expression of IL-6 by immunohistochemistry in human muscle tissue from biopsies obtained at time points 0, 3, 4.5, 6, 9, and 24 h in relation to 3 h of bicycle exercise performed by healthy young males (n=12) and in resting controls (n=6). The IL-6 expression was clearly increased after exercise and remained high even by 24 h, relative to preexercise or resting individuals. The IL-6 immunostainings of skeletal muscle cells were homogeneous and without difference between muscle fiber types. The IL-6 mRNA peaked immediately after the exercise, and, in accordance, the IL-6 protein expression within muscle cells was most pronounced around 3 h post-exercise. However, the finding that plasma IL-6 concentration peaked in the end of exercise indicates a high turnover of muscle-derived IL-6. In conclusion, the finding of marked IL-6 protein expression exclusively within skeletal muscle fibers following exercise demonstrates that skeletal muscle fibers of all types are the dominant cell source of exercise-induced release of IL-6 from working muscle.
Journal of Applied Physiology, 2005
The cytokine interleukin-6 (IL-6) exerts it actions via the IL-6 receptor (IL-6R) in conjunction with the ubiquitously expressed gp130 receptor. IL-6 is tightly regulated in response to exercise, being affected by factors such as exercise intensity and duration, as well as energy availability. Although the IL-6 response to exercise has been extensively studied, little is known about the regulation of the IL-6R response. In the present study, we aimed to investigate the effect of exercise, training, and glycogen availability, factors known to affect IL-6, on the regulation of gene expression of the IL-6R in human skeletal muscle. Human subjects performed either 10 wk of training with an acute exercise bout before and after the training period, or a low-glycogen vs. normal-glycogen acute exercise trial. The IL-6R mRNA response was evaluated in both trials. In response to acute exercise, an increase in IL-6R mRNA levels was observed. Neither training nor intramuscular glycogen levels had an effect on the IL-6R mRNA response to exercise. However, after 10 wk of training, the skeletal muscle expressed a higher mRNA level of IL-6R compared with before training. The present study demonstrated that the IL-6R gene expression levels in skeletal muscle are increased in response to acute exercise, a response that is very well conserved, being affected by neither training status nor intramuscular glycogen levels, as opposed to IL-6. However, after the training period, IL-6R mRNA production was increased in skeletal muscle, suggesting a sensitization of skeletal muscle to IL-6 at rest. interleukin-6 receptor CYTOKINES EXERT THEIR ACTIONS via specific receptors, which by themselves can be regulated via local and systemic factors. One of these cytokine and receptor systems is the IL-6/IL-6 receptor (IL-6R) system. IL-6 has various roles in immune function, but it is also produced in response to acute exercise, where it serves a metabolic role. Thus an infusion of IL-6 results in increased lipolysis and oxidation rate (32) and increases hepatic glucose production during exercise (6). IL-6 also increases the insulin-stimulated glucose uptake in myocytes, indicating an autocrine role on the skeletal muscle (2). The expression of IL-6 is tightly regulated during an acute exercise bout. Its regulation in skeletal muscle depends on exercise intensity and duration, as well as energy availability such as intramuscular glycogen and blood glucose levels (7,
AJP: Endocrinology and Metabolism, 2004
Contracting skeletal muscle expresses large amounts of IL-6. Because 1) IL-6 mRNA expression in contracting skeletal muscle is enhanced by low muscle glycogen content, and 2) IL-6 increases lipolysis and oxidation of fatty acids, we hypothesized that regular exercise training, associated with increased levels of resting muscle glycogen and enhanced capacity to oxidize fatty acids, would lead to a less-pronounced increase of skeletal muscle IL-6 mRNA in response to acute exercise. Thus, before and after 10 wk of knee extensor endurance training, skeletal muscle IL-6 mRNA expression was determined in young healthy men ( n = 7) in response to 3 h of dynamic knee extensor exercise, using the same relative workload. Maximal power output, time to exhaustion during submaximal exercise, resting muscle glycogen content, and citrate synthase and 3-hydroxyacyl-CoA dehydrogenase enzyme activity were all significantly enhanced by training. IL-6 mRNA expression in resting skeletal muscle did not ...
Increase in interstitial interleukin-6 of human skeletal muscle with repetitive low-force exercise
Journal of Applied Physiology, 2004
Interleukin-6 (IL-6), which is released from muscle tissue during intense exercise, possesses important metabolic and probably anti-inflammatory properties. To evaluate the IL-6 response to low-intensity exercise we conducted two studies: I) a control study with insertion of microdialysis catheters in muscle and determination of interstitial muscle IL-6 response over two hours of rest and II) an exercise study to investigate the IL-6 response to 20 min repetitive low-force exercise. In both studies a microdialysis catheter (cut-off 3000 kDa) was inserted into the upper trapezius muscle of 6 male subjects and the catheters were perfused with ringer-acetat at 5 µl min -1 . Venous plasma samples were taken in the exercise study.
Interleukin-6 Kinetics in Blood After Acute Exercise: Mechanisms and Clinical Implications (Atena Editora), 2024
Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in regulating immune and metabolic responses to exercise. This literature review examines the kinetics of IL-6 in the blood after acute exercise sessions, highlighting the main factors that influence its release, such as the type of exercise, intensity, duration and energy supplementation. The studies reviewed indicate that long-term aerobic exercise tends to cause more significant increases in IL-6 levels compared to resistance exercise. In addition, carbohydrate ingestion during exercise can attenuate IL-6 elevation, while fasted exercise amplifies this response. The clinical implications of these findings are discussed, especially in relation to the use of exercise as a therapeutic strategy to modulate the inflammatory state in individuals with chronic conditions. The review concludes that IL-6 is an essential mediator of adaptations to exercise and suggests directions for future research in the area.
Cell Stress and Chaperones, 2010
As interleukin-6 (IL-6), its soluble receptor (sIL-6R), and the IL-6/sIL-6R complex is transiently elevated in response to prolonged moderate-intensity exercise, this study investigated how these levels would be modulated by an acute bout of high-intensity intermittent (HIIT) exercise in comparison to continuous moderate-intensity exercise (MOD). This study also investigated the expression of the differentially spliced sIL-6R (DS-sIL-6R) in response to exercise. Eleven healthy males completed two exercise trials matched for external work done (582±82 kJ). During MOD, participants cycled at 61.8 (2.6)% VO 2peak for 58.7 (1.9) min, while HIIT consisted of ten 4-min intervals cycling at 87.5 (3.4)% : V O 2peak separated by 2-min rest. Blood samples were collected pre-exercise, post-exercise, and 1.5, 6, and 23 h post-exercise. Plasma IL-6, sIL-6R, IL-6/sIL-6R complex, and DS-sIL-6R levels were measured by enzyme-linked immunosorbent assay. HIIT caused a significantly greater increase in IL-6 than MOD (P= 0.018). Both MOD and HIIT resulted in an increase in sIL-6R and IL-6/sIL-6R complex (P<0.001), however, this was not significantly different between trials. Soluble IL-6R peaked at 6 h post-exercise in both trials. DS-sIL-6R increased significantly with exercise (P=0.02), representing 0.49% of the total sIL-6R increase. This investi-gation has demonstrated that the IL-6 response is greater after intermittent high-intensity exercise than comparable moderate-intensity exercise; however, increased IL-6/sIL-6R complex nor sIL-6R was different between HIIT and MOD. The current study has shown for the first time that elevated sIL-6R after HIIT exercise is derived from both proteolytic cleavage and differential splicing.