Exercise-induced Interleukin-6 Research Articles

Heat acclimation does not attenuate hepcidin elevation after a single session of endurance exercise under hot condition.

PurposeWe sought to determine the effects of heat acclimation on endurance exercise-induced hepcidin elevation under hot conditions.MethodsFifteen healthy men were divided into two groups: endurance training under hot conditions (HOT, 35 °C, n = 8) and endurance training under cool conditions (CON, 18 °C, n = 7). All subjects completed 10 days of endurance training (8 sessions in total), consisting of 60 min of continuous exercise at 50% of maximal oxygen uptake (dot{V}{text{O}}_{2max }) under their assigned environment condition. Subjects completed a heat stress exercise test (HST, 60 min exercise at 60% dot{V}{text{O}}_{2max }) to evaluate the exercise-induced thermoregulatory and hepcidin responses under hot conditions (35 °C) before (pre-HST) and after (post-HST) the training period.ResultsCore temperature during exercise in the post-HST decreased significantly in the HOT group compared to pre-HST (P = 0.004), but not in the CON group. The HOT and CON groups showed augmented exercise-induced plasma interleukin-6 (IL-6) elevation in the pre-HST (P = 0.002). Both groups had significantly attenuated increases in exercise-induced IL-6 in the post-HST; however, the reduction of exercise-induced IL-6 elevation was not different significantly between both groups. Serum hepcidin concentrations increased significantly in the pre-HST and post-HST in both groups (P = 0.001), no significant difference was observed between both groups during each test or over the study period.Conclusion10 days of endurance training period under hot conditions improved thermoregulation, whereas exercise-induced hepcidin elevation under hot conditions was not attenuated following the training.

Acute Resistance Exercise at Varying Volume Loads Does Not Enhance Plasma Interleukin-6

Background: Aerobic exercise has been shown to impart anti-inflammatory effects partly through increased secretion of interleukin-6 (IL-6). Still unclear, however, is whether resistance exercise (RE) also enhances IL-6 secretion. Objective: The present study aimed to examine the effect of RE, performed at varying volume loads (VL), on plasma IL-6. Methods: Ten subjects (seven males and three females: age 37.9 ± 11.4 years; height 170.81 ± 11.16 cm; weight 71.36 ± 11.26 Kg.) participated in three randomized RE protocols: high VL (HVL) (5 sets x 20 repetitions at 45% 1-repetition maximum (1-RM), medium VL (MVL) (3x12 at 75% 1-RM), and low VL (LVL) (2x4 at 90% 1-RM) each separated by 96 hours. Capillary blood for IL-6 measurements was drawn immediately pre-exercise, immediately post-exercise, and 1- and 2-hours post-exercise. Results: There were no significant differences in plasma IL-6 between exercise condition (LVL, MVL, HVL) or at any time point (p=0.422 and p=0.870, respectively). Conclusion: Plasma IL-6 levels are not acutely sensitive to RE, regardless of volume load; therefore, any reported anti-inflammatory effect of RE appears to operate outside of the exercise-induced IL-6 pathway.

Acid sphingomyelinase inhibition alleviates muscle damage in gastrocnemius after acute strenuous exercise.

[Purpose]Strenuous exercise often induces skeletal muscle damage, which results in impaired performance. Sphingolipid metabolism contributes to various cellular processes, including apoptosis, stress response, and inflammation. However, the relationship between exercise-induced muscle damage and ceramide (a key component of sphingolipid metabolism), is rarely studied. The present study aimed to explore the regulatory role of sphingolipid metabolism in exercise-induced muscle damage.[Methods]Mice were subjected to strenuous exercise by treadmill running with gradual increase in intensity. The blood and gastrocnemius muscles (white and red portion) were collected immediately after and 24 h post exercise. For 3 days, imipramine was intraperitoneally injected 1 h prior to treadmill running.[Results]Interleukin 6 (IL-6) and serum creatine kinase (CK) levels were enhanced immediately after and 24 h post exercise (relative to those of resting), respectively. Acidic sphingomyelinase (A-SMase) protein expression in gastrocnemius muscles was significantly augmented by exercise, unlike, serine palmitoyltransferase-1 (SPT-1) and neutral sphingomyelinase (N-SMase) expressions. Furthermore, imipramine (a selective A-SMase inhibitor) treatment reduced the exercise-induced CK and IL-6 elevations, along with a decrease in cleaved caspase-3 (Cas-3) of gastrocnemius muscles.[Conclusion]We found the crucial role of A-SMase in exercise-induced muscle damage.

Exhaustive acute exercise-induced ER stress is attenuated in IL-6-knockout mice.

The endoplasmic reticulum (ER) stress and inflammation relationship occurs at different levels and is essential for the adequate homeostatic function of cellular systems, becoming harmful when chronically engaged. Intense physical exercise enhances serum levels of interleukin 6 (IL-6). In response to a chronic exhaustive physical exercise protocol, our research group verified an increase of the IL-6 concentration and ER stress proteins in extensor digitorium longus (EDL) and soleus. Based on these results, we hypothesized that IL-6-knockout mice would demonstrate a lower modulation in the ER stress proteins compared to the wild-type mice. To clarify the relationship between exercise-induced IL-6 increased and ER stress, we studied the effects of an acute exhaustive physical exercise protocol on the levels of ER stress proteins in the skeletal muscles of IL-6-knockout (KO) mice. The WT group displayed a higher exhaustion time compared to the IL-6 KO group. After 1 h of the acute exercise protocol, the serum levels of IL-6 and IL-10 were enhanced in the WT group. Independent of the experimental group, the CHOP and cleaved caspase 12/total caspase 12 ratio in EDL as well as ATF6 and CHOP in soleus were sensitive to the acute exercise protocol. Compared to the WT group, the oscillation patterns over time of BiP in EDL and soleus as well as of peIF2-alpha/eIF2-alpha ratio in soleus were attenuated for the IL-6 KO group. In conclusion, IL-6 seems to be related with the ER stress homeostasis, once knockout mice presented attenuation of BiP in EDL and soleus as well as of pEiF2-alpha/EiF2-alpha ratio in soleus after the acute exhaustive physical exercise protocol.

Effect of martial arts training on IL-6 and other immunological parameters among Trinidadian subjects.

Persistent bouts of extended exercise and heavy training are associated with depressed immune cell function. It has recently been demonstrated that interleukin-6 (IL-6) is produced locally in contracting skeletal muscles and acts on a wide range of tissues. Larger amounts of IL-6 are produced in response to exercise than any other cytokines. Though the majority of existing data obtained following prolonged exercise, it remains to be explained the effect of martial arts training on IL-6 and other immunological parameters and associated changes to the duration of this type of exercise. IL-1α is produced mainly by activated macrophages, as well as neutrophils, epithelial cells, and endothelial cells. It possesses metabolic, physiological, hematopoietic activities, and plays one of the central roles in the regulation of the immune responses. This study aimed to evaluate the effect of martial arts training on IL-6 and other immunological parameters among Trinidadian subjects. Sixteen healthy, non-smoker individuals who have been martial arts practitioners for the last 5-15 years, aged 25.94±7.6.20 years. Blood samples were collected to determine IL-6 and other immunological parameters at pre-exercise, immediately post exercise (0 hours), 1 hour, 2 hour and 52 hours of post exercise). IL-6 and IL-1 was measured using Human IL-6 and IL-1 β ELISA kit, blood cell count was done using automated blood cell counter and CD4, and CD3 count was performed using the automated immunofluorescence analysis by flow cytometer. The mean basal IL-6 level was 71.47±4.3 and reduced to 70.1±21.6 immediately after exercise and then increased to 75.70±8.2 after one hour of exercise bout, returning to basal level after two hours and remained so after 52 hours. The CD4 count was decreased as low as 102.2, (much lower than immune-compromised subjects) after the bout of training but returned to normal range within 2 hours of exercise and increased even more after 52 hours. Similar trends have been observed for hematological parameters such as white blood cells, granulocytes and lymphocytes. The white blood cell count, granulocyte count and lymphocyte count increased immediately after exercise and returned to basal level only after 52 hours of exercise. This study highlights that the martial arts exercise increases key cytokines and other hematological parameters. The magnitude of the martial arts exercise-induced IL-6 response is dependent on intensity and especially duration of the exercise.

Exercise-Induced Interleukin-6 and Metabolic Responses in Hot, Temperate, and Cold Conditions

The purpose of this study was to determine the effects of exercise in hot, cold, and temperate environments on plasma interleukin-6 (IL-6). Eleven recreationally trained males (age = 25 ± 4 years, height = 178 ± 5 cm, weight = 79.4 ± 13.5 kg, body fat = 14.7 ± 3.6%, VO2 peak = 54.6 ± 11.5 ml kg-1 min-1) performed a 1 hr cycling bout in hot (33 °C), cold (7 °C), and temperate (20 °C) environments at 60% of Wmax followed by 3 hr of supine recovery in temperate conditions. Expired gases were measured every 15 min during exercise and once every hour during recovery. Heart rate was continuously measured throughout the trials. Blood samples were obtained from the antecubital vein pre-exercise, immediately post-exercise, and 3 hr post-exercise. Blood samples were analyzed for plasma concentrations of IL-6 using a commercial ELISA kit. Plasma IL-6 concentrations were significantly higher immediately post-exercise (14.8 ± 1.6 pg ml-1, p = 0.008) and 3 hr post-exercise (14.8 ± 0.9 pg ml-1, p = 0.018) compared to pre-exercise (11.4 ± 2.4 pg ml-1), across all trials. There were no differences in plasma IL-6 concentrations (p = 0.207) between temperature conditions.Oxygen consumption and heart rate were higher and respiratory exchange ratio was lower in the hot compared to other conditions (p < 0.05). These data indicate that the temperature in which exercise occurs does not affect acute plasma IL-6 response despite differences in metabolic state.

Cardiovascular Response and Serum Interleukin-6 Level in Concentric Vs. Eccentric Exercise.

Cardiovascular Disease (CVD) is a leading cause of morbidity and mortality in India. Resistance exercise is strongly recommended for implementation in CVD prevention programs. Dynamic resistance exercise comprises of concentric (muscle shortening) and eccentric (muscle lengthening) phase. The contraction of skeletal muscle promotes the synthesis and secretion of cytokines and peptides from myocytes, known as 'myokines'. Interleukin-6 (IL-6) is the first myokine to be released in the blood in response to exercise. To compare the cardiovascular response and serum IL-6 level in concentric and eccentric exercise done at same absolute workload. In this non-randomised crossover study 24, apparently healthy and young male adults performed an acute bout of concentric and eccentric exercise. Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Heart Rate (HR), Mean Arterial Pressure (MAP), Pulse Pressure (PP) and serum IL-6 were measured just before and immediately after exercise. Paired t-test or Wilcoxon signed-rank test were applied to compare the data within-group and in-between group. SBP, HR, MAP, PP, DBP and IL-6 level increased significantly after both, concentric and eccentric exercise. The mean change in SBP, HR, MAP, PP, and IL-6 after concentric exercise (18.54±3.06, 57.21±10.73, 8.35±1.40, 15.25±5.29, 5.40±3.13 respectively) was significantly higher than after eccentric exercise (13.38±1.72, 43.25±8.34, 6.50±1.0, 10.21±3.16, 4.36±2.54 respectively). A non-significant rise in DBP was obtained after concentric exercise (3.25±2.79) as compared to eccentric exercise (3.08±1.89). Eccentric exercise not only caused a lesser cardiovascular demand as compared to concentric exercise but also a significant increment in IL-6 level. Exercise-induced IL-6 may prevent the initiation and development of CVD. Hence, eccentric exercise training might be recommended for reducing morbidity and mortality in individuals with- or at a risk of developing CVD.

Exercise-Induced Transient Increase in IL-6 Stimulates GLUT4 Expression and Enhances Insulin Sensitivity in Mouse Skeletal Muscle

A single bout of exercise induces transient increase in blood interleukin-6 (IL-6) level in human and rodents, however, the role of exercise-induced IL-6 is poorly understand. Prolonged, chronic increase in IL-6 reflects low-grade inflammation, which decrease insulin sensitivity in adipose tissue, liver and skeletal muscle. On the other hand, acute, short-period of IL-6 enhances insulin sensitivity. Because, the increase in IL-6 after exercise is transient, we hypothesized that transient increase in IL-6 after exercise enhances insulin sensitivity in skeletal muscle. C57BL6J mouse were i.v. injected normal IgG or IL-6 antibody before exercise. Twenty-four hours after a single bout of exercise (treadmill running: 20 m/min, 90 min with 10 degree incline), plantaris muscle was harvested and incubated in oxygenized KRB buffer to measure insulin-stimulated 2-deoxyglucose (2-DG) uptake. Compared with sedentary mouse, insulin-stimulated 2-DG uptake in plantaris muscle was increased 24 h after exercise in IgG-injected mouse, however, the increase induced by exercise was not observed in IL-6 antibody-injected mouse. Concomitant with this results, GLUT4 expression was increased 24 h after exercise in IgG-injected mouse, the increase was canceled in IL-6 antibody-injected mouse. Recombinant mouse IL-6 injection increased GLUT4 expression both fast-twitch plantaris muscle and slow-twitch soleus muscle in C57BL6J mouse. Furthermore, short period incubation of IL-6 (3-12 hours) increased GLUT4 expression in differentiated C2C12 myotubes, however long period (24 h) did not. These results suggests that exercise-induced transient increase in IL-6 affects skeletal muscle in autocrine/paracrine manner, which enhances GLUT4 expression leading to increase insulin sensitivity in skeletal muscle.

Interleukin-6 mediates exercise preconditioning against myocardial ischemia reperfusion injury.

Interleukin-6 (IL-6) is a pleiotropic cytokine that protects against cardiac ischemia-reperfusion (I/R) injury following pharmacological and ischemic preconditioning (IPC), but the affiliated role in exercise preconditioning is unknown. Our study purpose was to characterize exercise-induced IL-6 cardiac signaling (aim 1) and evaluate myocardial preconditioning (aim 2). In aim 1, C57 and IL-6(-/-) mice underwent 3 days of treadmill exercise for 60 min/day at 18 m/min. Serum, gastrocnemius, and heart were collected preexercise, immediately postxercise, and 30 and 60 min following the final exercise session and analyzed for indexes of IL-6 signaling. For aim 2, a separate cohort of exercise-preconditioned (C57 EX and IL-6(-/-) EX) and sedentary (C57 SED and IL-6(-/-) SED) mice received surgical I/R injury (30 min I, 120 min R) or a time-matched sham operation. Ischemic and perfused tissues were examined for necrosis, apoptosis, and autophagy. In aim 1, serum IL-6 and IL-6 receptor (IL-6R), gastrocnemius, and myocardial IL-6R were increased following exercise in C57 mice only. Phosphorylated (p) signal transducer and activator of transcription 3 was increased in gastrocnemius and heart in C57 and IL-6(-/-) mice postexercise, whereas myocardial iNOS and cyclooxygenase-2 were unchanged in the exercised myocardium. Exercise protected C57 EX mice against I/R-induced arrhythmias and necrosis, whereas arrhythmia score and infarct outcomes were higher in C57 SED, IL-6(-/-) SED, and IL-6(-/-) EX mice compared with SH. C57 EX mice expressed increased p-p44/42 MAPK (Thr(202)/Tyr(204)) and p-p38 MAPK (Thr(180)/Tyr(182)) compared with IL-6(-/-) EX mice, suggesting pathway involvement in exercise preconditioning. Findings indicate exercise exerts cardioprotection via IL-6 and strongly implicates protective signaling originating from the exercised skeletal muscle.

Increase in interleukin-6 immediately after wheelchair basketball games in persons with spinal cord injury: preliminary report

Case series. To investigate the effects of wheelchair basketball game on plasma interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and blood cell counts in persons with spinal cord injury (SCI). The 2009 Mei-shin League of Wheelchair Basketball Games held at Wakayama, Japan. Five wheelchair basketball players with SCI voluntarily participated in this study. Blood samples were taken approximately 1 h before the player warm-up for the game and immediately after the game. IL-6, TNF-α, CRP and blood cell count were measured. Plasma IL-6 level and number of monocytes were significantly increased after the game, compared with pre-game measurements (P<0.05). No changes were observed in other measurements. There was a significant relationship between increased IL-6 levels and accumulated play duration. The lack of change in TNF-α and CRP levels suggested that the exercise-induced rise in IL-6 was not related to exercise-induced inflammatory response. Furthermore, the associated increase in the number of monocytes did not correlate with exercise-induced IL-6 changes, negating monocytes as the source of IL-6.

Elimination of Eccentric Exercise-Induced Interleukin-6 Response by Heat Preconditioning

Exercise training lowers the mortality rate of animals under heat stress. It is currently unknown whether heat preconditioning can attenuate exercise-induced increases in circulating interleukin-6 (IL-6) for athletes. Sixteen male basketball players were randomly assigned to the control (n = 8) and heat preconditioning (n = 8) groups. The heat preconditioning program consisted of a 30-min hot water immersion at 41°C performed every 72 h up to 4 sessions, which slightly elevated circulating creatine kinase (CK) and thiobarbituric acid-reactive substances (TBARS) by 27% and 21%, respectively (P ＜ 0.05). Seventy two hours after the last hot water immersion, both groups were challenged with an acute bout of eccentric exercise (6 squats at 85% maximal voluntary effort for 6 sets), which elicited significant increases in IL-6 (+120%) and CK (+34%) above pre-exercise level of the control group (P ＜ 0.05). This increase was absent in the heat preconditioning group. Heart rate variability (HRV) and high frequency power (HF) were increased following heat preconditioning, and remained elevated after exercise challenge. Our study provides evidence that eccentric exercise-induced stress response can be attenuated by a heat preconditioning protocol at 41°C.

Non‐invasive ventilation abolishes the IL‐6 response to exercise in muscle‐wasted COPD patients: A pilot study

Systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) has been related to the development of comorbidities. The level of systemic inflammatory mediators is aggravated as a response to exercise in these patients. The aim of this study was to investigate whether unloading of the respiratory muscles attenuates the inflammatory response to exercise in COPD patients. In a cross-over design, eight muscle-wasted stable COPD patients performed 40 W constant work-rate cycle exercise with and without non-invasive ventilation support (NIV vs control). Patients exercised until symptom limitation for maximally 20 min. Blood samples were taken at rest and at isotime or immediately after exercise. Duration of control and NIV-supported exercise was similar, both 12.9 ± 2.8 min. Interleukin- 6 (IL-6) plasma levels increased significantly by 25 ± 9% in response to control exercise, but not in response to NIV-supported exercise. Leukocyte concentrations increased similarly after control and NIV-supported exercise by ∼15%. Plasma concentrations of C-reactive protein, carbonylated proteins, and production of reactive oxygen species by blood cells were not affected by both exercise modes. This study demonstrates that NIV abolishes the IL-6 response to exercise in muscle-wasted patients with COPD. These data suggest that the respiratory muscles contribute to exercise-induced IL-6 release in these patients.

Is Activation Of The HPA Axis During High Intensity Cycling Mediated By Interleukin-6?

Interleukin-6 (IL-6) is secreted by skeletal muscle(s) into the circulation during and after exercise; however, the extent of this response to high intensity exercise is unclear. This myokine appears to regulate the availability and use of energy substrates in contracting muscles and also can activate the hypothalamic-pituitary-adrenal (HPA) axis. PURPOSE: To characterize IL-6 release and HPA axis activation in response to high intensity cycling. METHODS: Collegiate physically active subjects (n=9) performed two cycle ergometer tests of equal total duration and work. The 14 min high intensity test (HI) consisted of 4×30s Wingate tests, each separated by 4 min of recovery while cycling at 20 W. The total work performed during the HI test was equally distributed over a continuous 14 min low intensity test (LI) ∼48 hr later. Blood was collected from an indwelling venous catheter pre-, during (1.5, 6, and 10.5 min), and postexercise (+1, +15, +30, +60 min; +48 hr). Plasma volume (PV) shifts from preexercise were estimated using hemoglobin and hematocrit levels and used to correct hormone concentrations. IL-6 and cortisol concentrations were measured by chemiluminescent immunoassay and were corrected for PV shifts. Resting and exercise hormone concentrations were evaluated using repeated measures ANOVA. RESULTS: Mean (SD) plasma IL-6 peaked postexercise in both protocols: +60 min in HI (1.69(0.75) pg/ml) and +30 min in LI (1.26(0.96) pg/ml) and were similar to preexercise levels. Cortisol changes in response to exercise differed between protocols (main effect: p= 0.06; interaction: p= 0.04). In both protocols cortisol declined during exercise; however, an opposing response was apparent from 10.5 min to +1 min (p=0.10) with an increase in HI (21.7(6.9) to 22.6(5.9) ug/L) and decrease in LI (20.1(6.5) to 17.7(3.9) ug/L). After +1 min HI and LI cortisol continued to decline postexercise. HI+48 hr cortisol levels were lower at rest/LI preexercise (HI pre= 24.5(4.8) ug/L; LI pre=21.6(5.6) ug/L; p=0.07) and during the LI protocol (p< 0.0001). CONCLUSION: Although high intensity exercise had a minimal effect on exercise-induced IL-6, cortisol responses suggest some degree of HPA axis activation. Ongoing ACTH analysis will help to further characterize the extent of this activation in response to high intensity cycling.

Effects of mode and intensity on the acute exercise-induced IL-6 and CRP responses in a sedentary, overweight population

This study sought to compare the respective effects of resistance or aerobic exercise of higher or lower intensities on the acute plasma interleukin-6 (IL-6) and C-reactive protein (CRP) response in a sedentary, middle-aged, disease-free cohort. Following baseline testing, and in a randomized cross-over design, 12 sedentary males completed four exercise protocols, including 40 min of moderate-vigorous (M-VA) or low-intensity (LA) aerobic exercise on a cycle ergometer; and a moderate-vigorous (M-VR) or low-intensity (LR) full-body resistance session matched for protocol duration. Venous blood was obtained pre-, post-, 3 h post and 24 h post-exercise and analysed for IL-6, CRP, leukocyte count, myoglobin, creatine kinase (CK), and cortisol. Diet and physical activity were standardized 24 h before and after exercise. Results indicated an elevated CRP response in the M-VR protocol in comparison to the low-intensity protocols (P < 0.05); however, no changes were evident between the moderate-vigorous intensity protocols. The moderate-vigorous intensity protocols induced significant increases of IL-6, cortisol, and leukocytes in comparison to the low-intensity protocols (P < 0.05). However, the IL-6 response showed no significant differences between the moderate-vigorous intensity protocols, despite the M-VR protocol inducing the largest response of markers indicative of muscle damage (CK, myoglobin, and neutrophil count) (P < 0.05). Hence, indicating a disassociation between the IL-6 response and markers of muscle damage within the respective exercise bouts. The highest IL-6 response was evident in the moderate-vigorous intensity protocols immediately post-exercise. Moreover, the exercise modality did not seem to influence the acute IL-6 and CRP response, with the main determinant of the IL-6 response being exercise intensity.

Role of Antioxidant Supplementation on Training-induced IL-6

Antioxidant supplementation has been shown to attenuate the acute exercise-induced increase in plasma interleukin-6 (IL-6). PURPOSE: To investigate the effect of antioxidants on the regulation of IL-6 expression in muscle and circulation in response to acute exercise before and after high-intensity endurance exercise training. METHODS: Twenty-one young healthy men were allocated into either an antioxidant (AO; vitamin C and E) or a placebo (PL) group. A 1h-acute bicycling exercise trial at 65% of maximal power output was performed before and after 12 weeks of progressive endurance exercise training. Blood samples and muscle biopsies were taken pre and immediately after cessation of exercise, and at 3h of recovery period. RESULTS: The acute exercise-induced plasma IL-6 increase was blunted after the training period in the PL group (P<0.05) but not in the AO group. Endurance exercise training lowered resting levels and attenuated the acute exercise-induced increase in muscle-IL-6 mRNA in both groups. There was an overall increase in skeletal muscle oxidative stress as evaluated by malondialdehyde (MDA) with training in the AO group compared with PL (P<0.05). This was accompanied by a general increase in skeletal muscle mRNA expression of antioxidative enzymes, including catalase (CAT), copper-zinc superoxide dismutase (CuZnSOD) and glutathione peroxidase 1 (GPX1) mRNA expression in the AO group. However, skeletal muscle protein content of catalase, CuZnSOD, or GPX1 was not affected by training or supplementation. CONCLUSIONS: Vitamin C and E supplementation blunts the training-induced lowering of exercise-induced increase in plasma IL-6, possibly through increased oxidative stress in the trained state.

Effects of allicin supplementation on plasma markers of exercise-induced muscle damage, IL-6 and antioxidant capacity

To investigate the effects of allicin supplementation on exercise-induced muscle damage (EIMD), interleukin-6 (IL-6), and antioxidative capacity, a double-blinded, placebo-controlled study was conducted in well-trained athletes. Subjects were randomly assigned to an allicin supplementation group (AS group) and a control group, and received either allicin or placebo for 14 days before and 2 days after a downhill treadmill run. Plasma creatine kinase (CK), muscle-specific creatine kinase (CK-MM), lactate dehydrogenase (LDH), IL-6, superoxide dismutase (SOD), total antioxidative capacity (TAC), and perceived muscle soreness were measured pre and post exercise. AS group had significantly lower plasma levels of CK, CK-MM and IL-6, and reduced perceived muscle soreness after exercise, when compared with the control group. AS group also demonstrated a trend toward reducing plasma concentration of LDH after exercise (P = 0.08), although not statistically significant. Allicin supplementation induced a higher value of TAC at rest, and this higher value was maintained 48 h after exercise, however, there was no difference in SOD values after exercise between the two groups. The results suggested that allicin might be a potential agent to reduce EIMD. Further studies concerning anti-inflammatory and anti-oxidative effects of allicin on EIMD are needed.

Contraction‐induced interleukin‐6 transcription in rat slow‐type muscle is partly dependent on calcineurin activation

The present work aimed at determining whether interleukin-6 (IL-6) produced by skeletal muscle during exercise is related, at least partly, to calcineurin activity. Rats were treated with two specific calcineurin inhibitors, cyclosporin A (CsA) and FK506, or vehicle (Vhl); they were then subjected to exhaustive treadmill running. Modulatory Calcineurin-Interacting Protein-1 (MCIP-1) mRNA levels, a reliable indicator of calcineurin activity, and IL-6 mRNA levels were measured by real-time RT-PCR in soleus muscles, and IL-6 protein concentration was measured in the plasma. Because low carbohydrates availability enhances IL-6 transcription through p38 Mitogen Activated Protein Kinase (MAPK) pathway, muscle glycogen content and glycaemia were measured and p38 MAPK phosphorylation was determined in skeletal muscle by western blotting. As expected, exercise induced an increase in IL-6 (P < 0.01) and MCIP-1 mRNA (P < 0.01) in soleus muscle of Vhl rats, and enhanced p38 phosphorylation and plasmatic IL-6 protein (P < 0.05). Calcineurin inhibition did not affect running time, glycemia or soleus glycogen content. CsA administration totally inhibited the exercise-induced increase in MCIP-1 mRNA (P < 0.01), blunted the IL-6 gene transcription related to muscle activity, and suppressed the changes in IL-6 protein in plasma. In addition to its inhibition of calcineurin activity, FK506 administration totally suppressed the exercise-induced IL-6 gene transcription, likely by an inhibition of p38 activation. Taken together, these results demonstrate that in addition to p38 MAPK, increased calcineurin activity is one of the signalling events involved in IL-6 gene transcription.

Carbohydrate Influences Plasma Interleukin-6 but Not C-Reactive Protein or Creatine Kinase Following a 32-Km Mountain Trail Race

Attenuation of exercise-induced interleukin-6 (IL-6) responses by carbohydrate (CHO) has been demonstrated in studies comparing controlled doses (> or = 0.9 g x kg(-1) x h(-1)) to placebo, but not in studies of voluntary intake. This study sought to determine if attenuation of the IL-6 response during a 32.2-km mountain trail race occurs for high compared to low ad libitum CHO intakes. IL-6, C-reactive protein (CRP), and creatine kinase activity (CK) were analyzed from blood samples collected 12 h pre-, 0, 4, and 24 h post-race. Subjects were grouped into low (n =14, 0.4 +/- 0.1 g x kg(-1) x h(-1)) and high (n =18, 0.8 +/- 0.2 g x kg(-1) x h(-1)) CHO intake groups. IL-6 0 h post-race (P < 0.05) was higher in the low (40.2 +/- 22.7 pg x mL(-1)) compared to the high CHO group (32.7 +/- 22.1 pg x mL(-1)). CRP and CK both increased post-race, but no differences were observed between groups. Attenuation of exercise-induced IL-6 is apparent across a range of CHO intakes.

Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content.

1. Prolonged exercise results in a progressive decline in glycogen content and a concomitant increase in the release of the cytokine interleukin-6 (IL-6) from contracting muscle. This study tests the hypothesis that the exercise-induced IL-6 release from contracting muscle is linked to the intramuscular glycogen availability. 2. Seven men performed 5 h of a two-legged knee-extensor exercise, with one leg with normal, and one leg with reduced, muscle glycogen content. Muscle biopsies were obtained before (pre-ex), immediately after (end-ex) and 3 h into recovery (3 h rec) from exercise in both legs. In addition, catheters were placed in one femoral artery and both femoral veins and blood was sampled from these catheters prior to exercise and at 1 h intervals during exercise and into recovery. 3. Pre-exercise glycogen content was lower in the glycogen-depleted leg compared with the control leg. Intramuscular IL-6 mRNA levels increased with exercise in both legs, but this increase was augmented in the leg having the lowest glycogen content at end-ex. The arterial plasma concentration of IL-6 increased from 0.6 +/- 0.1 ng x l(-1) pre-ex to 21.7 +/- 5.6 ng x l(-1) end-ex. The depleted leg had already released IL-6 after 1 h (4.38 +/- 2.80 ng x min(-1) (P < 0.05)), whereas no significant release was observed in the control leg (0.36 +/- 0.14 ng x min(-1)). A significant net IL-6 release was not observed until 2 h in the control leg. 4. This study demonstrates that glycogen availability is associated with alterations in the rate of IL-6 production and release in contracting skeletal muscle.