Effect of passive repetitive isokinetic training on cytokines and hormonal changes

It is well known that muscle strength and power are important factors in exercise. Plyometrics is designed to gain muscle strength and power in a shock method. The passive repetitive isokinetic (PRI) machine is developed for plyometrics. The present study aims to understand the effect of ten-week PRI training in different intensities on human plasma concentration cytokines as well as hormonal changes. Thirty young male subjects were enrolled into the ten-week PRI training program and were divided randomly into traditional, low- and high-intensity PRI training groups. Blood samples were obtained before, during, after and 1-, 2-, 3-, 5- and 7-day (D) post-training. The plasma concentrations of cytokines and hormones were measured by an enzyme-linked immunosorbent assay (ELISA). Elevated plasma IL-2 was found in the subjects in all the training programs. Significant increases of proinflammatory cytokines IL-1beta and TNF-alpha were observed at post 7 D in the high-intensity PRI training (29.5 +/- 4.4 and 515.8 +/- 127.1 pg/ml, respectively). No significance in differences in the plasma concentration of IL-6 was observed in the traditional and low-intensity PRI training. Significant elevation of IL-6 was found at post 5 D in high-intensity PRI training. Higher plasma IL-6 concentration was observed at post 3 and 5 D in high-intensity PRI training compared to low-intensity PRI training (P < 0.05). Significant elevation of plasma IL-15 during (week 6) and after (post 0 D) was observed in low-intensity PRI training. Also, there were differences between low-intensity PRI training and traditional training at post 0, 2, 3, and 5 D. The plasma concentration of cortisol was decreased to the lowest value (118.0 +/- 17.3 ng/ml) at post 0 D in traditional training, then returned to the baseline (220.5 +/- 19.1 ng/ml). In the high-intensity PRI training, but not in the low-intensity PRI training, the cortisol level dropped from 224.9 +/- 25.8 ng/ml at post 0 D down to the 123.2 +/- 22.6 ng/ml at post 1 D. Significant differences were found at post 1 and 5 D between low- and high-intensity PRI training, and post 0, 1, 2, and 3 D between traditional and high-intensity PRI training. Significant increased testosterone was found post 0, 1, 2, and 3 D in traditional training. Higher plasma testosterone was observed during and the recovery period in low-intensity, but not in high-intensity, PRI training. In conclusion, high-intensity PRI training could induce the proinflammatory cytokines, i.e., IL-1beta and TNF-alpha, and decrease plasma cortisol in the recovery period.     

Cytokine response to strenuous exercise in athletes and non-athletes--an adaptive response

Exercise and physical strenuous activity have been demonstrated to increase the serum TNF-alpha and IL-6. Regular physical training is expected to attenuate such a response. This study was undertaken to understand the impact of regular exercise training on IL-6 and TNF-alpha in athletes and non-athletes. Ten athletes, who have been on regular training for the past 6 months, and 10 age- and sex-matched subjects (non-athlete group) who had no practice of regular exercise, were recruited. Both were subjected to undergo the same frequency level of strenuous exercise. Blood samples were collected; one before strenuous exercise and the other after the exercise. Plasma cytokines, IL-6 and TNF-alpha, were estimated using Sandwich ELISA method. All participants in the study were male with the athletes' age being 18.00+/-1.3years (mean+/-SD) and the non-athletes were aged 20.00+/-0.6years (mean+/-SD). Majority of the athletes and non-athletes demonstrated a rise in IL-6 and a fall in TNF-alpha levels. Further, the athletes showed a lesser magnitude of change in the cytokine levels following a longer duration of exercise than non-athletes. Athletes appear to have an attenuated cytokine response. Regular physical training has been demonstrated to attenuate the immune response to exercise in either direction.     

Serum levels of TNF-alpha,sIL-2R,IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet's disease

AIM: Behçet''s disease (BD) is asystemic immunoinflammatory disorder and the aetiopathogenesis is to be specified. Cytokines play a role in immune response and in many inflammatory diseases. The aim of this case-control study is to investigate serum pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta), soluble IL-2 receptor (sIL-2R), IL-6, and chemokine IL-8 levels in patients with BD. We also determined the end product of lipid peroxidation (malondialdehyde (MDA)) in BD patients as an index for oxidative stress. METHODS: A total of 37 patients (19 men, 18 women) with BD (active, n = 17; inactive, n = 20) and 20 age-matched and sex-matched healthy control subjects (11 men, nine women) included in this cross-sectional, blinded study. Serum TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels were determined by a spectrophotometer technique using the immulite chemiluminescent immunometric assay. Lipid peroxidation was evaluated by Wasowicz et aL The levels of cytokines and lipid peroxidation in the active period were compared with the inactive period of the disease. Results are expressed as mean +/- standard error. RESULTS: IL-1beta levels were below the detection limits of the assay (< 5 pg/ml) in all samples. Mean levels of MDA (8.1+/-0.7 micromol/l), sIL-2R (800+/-38 U/ml), IL-6 (12.6+/-1.1 pg/ml), IL-8 (7.2+/-0.4 pg/ml), and TNF-alpha (7.9+/-0.5 pg/ml) in active BD patients were significantly higher than those in inactive patients (4.3+/-0.5 micromol/l, p < 0.01; 447+/-16 U/ml, p < 0.001; 8.3+/-0.6 pg/ml, p = 0.006; 5.3+/-0.1 pg/ml, p < 0.001; and 5.1 0.2 pg/ml, p < 0.001; respectively) or control subjects (2.1+/-0.2 micromol/l, p < 0.001; 446+/-20 U/ml, p < 0.001; 6.4+/-0.2 pg/ml, p < 0.001; 5.4+/-0.1 pg/ml, p < 0.001; and 4.7+/-0.1 pg/ml, p < 0.001, respectively). On the contrary, only the mean IL-6 level was significantly different between inactive BD and control subjects (p = 0.02). All acute phase reactants were significantly higher in active BD than in inactive period (for each, p < 0.01). Conclusions: High levels of sIL-2R, IL-6, IL-8 and TNF-alpha indicate the activation of immune system in BD. Serum sIL-2R, IL-6, IL-8 and TNF-alpha seem to be related to disease activity. Increased lipid peroxidation suggests oxidative stress in BD and therefore tissue damage in such patients. Amelioration of clinical manifestations would be envisaged by targeting these cytokines, chemokines and lipid peroxidation with pharmacological agents.     

Impact of three different types of exercise on components of the inflammatory response

It was hypothesized that muscle injury would be greater with eccentric than with all-out or prolonged exercise, and that immune changes might provide an indication that supplements the information provided by traditional markers such as creatine kinase (CK) or delayed-onset muscle soreness. Eight healthy males [mean (SE): age = 24.9 (2.3) years, maximum oxygen consumption (VO2(max)) = 43.0 (3.1) ml x kg(-1) x min(-1)] were each assigned to four experimental conditions, one at a time, using a randomized-block design: 5 min of cycle ergometer exercise at 90% VO2(max) (AO), a standard circuit-training routine (CT), 2 h cycle ergometer exercise at 60% VO2(max) (Long), or remained seated for 5 h. Blood samples were analyzed for CK, natural killer (NK) cell counts (CD3(-)/CD16(+)56(+)), cytolytic activity and plasma levels of the cytokines interleukin (IL)-6, IL-10, and tissue necrosis factor alpha (TNF-alpha). CK levels were only elevated significantly 72 h following CT. NK cell counts increased significantly during all three types of exercise, but returned to pre-exercise baseline values within 3 h of recovery. Cytolytic activity per NK cell was not significantly modified by any type of exercise. Prolonged exercise induced significant increases in plasma IL-6 and TNF-alpha. We conclude that the lack of correlation between traditional markers of muscle injury (plasma CK concentrations and muscle soreness rankings) and immune markers of the inflammatory response suggests that, for the types and intensities of exercise examined in this study, the exercise-induced inflammatory response is modified by humoral and cardiovascular correlates of exercise.     

Voluntary exercise improves insulin sensitivity and adipose tissue inflammation in diet-induced obese mice

Exercise promotes weight loss and improves insulin sensitivity. However, the molecular mechanisms mediating its beneficial effects are not fully understood. Obesity correlates with increased production of inflammatory cytokines, which in turn, contributes to systemic insulin resistance. To test the hypothesis that exercise mitigates this inflammatory response, thereby improving insulin sensitivity, we developed a model of voluntary exercise in mice made obese by feeding of a high fat/high sucrose diet (HFD). Over four wk, mice fed chow gained 2.3 +/- 0.3 g, while HFD mice gained 6.8 +/- 0.5 g. After 4 wk, mice were subdivided into four groups: chow-no exercise, chow-exercise, HFD-no exercise, HFD-exercise and monitored for an additional 6 wk. Chow-no exercise and HFD-no exercise mice gained an additional 1.2 +/- 0.3 g and 3.3 +/- 0.5 g respectively. Exercising mice had higher food consumption, but did not gain additional weight. As expected, GTT and ITT showed impaired glucose tolerance and insulin resistance in HFD-no exercise mice. However, glucose tolerance improved significantly and insulin sensitivity was completely normalized in HFD-exercise animals. Furthermore, expression of TNF-alpha, MCP-1, PAI-1 and IKKbeta was increased in adipose tissue from HFD mice compared with chow mice, whereas exercise reversed the increased expression of these inflammatory cytokines. In contrast, expression of these cytokines in liver was unchanged among the four groups. These results suggest that exercise partially reduces adiposity, reverses insulin resistance and decreases adipose tissue inflammation in diet-induced obese mice, despite continued consumption of HFD.     

High tidal volume upregulates intrapulmonary cytokines in an in vivo mouse model of ventilator-induced lung injury.

Mechanical ventilation has been demonstrated to exacerbate lung injury, and a sufficiently high tidal volume can induce injury in otherwise healthy lungs. However, it remains controversial whether injurious ventilation per se, without preceding lung injury, can initiate cytokine-mediated pulmonary inflammation. To address this, we developed an in vivo mouse model of acute lung injury produced by high tidal volume (Vt) ventilation. Anesthetized C57BL6 mice were ventilated at high Vt (34.5 +/- 2.9 ml/kg, mean +/- SD) for a duration of 156 +/- 17 min until mean blood pressure fell below 45 mmHg (series 1); high Vt for 120 min (series 2); or low Vt (8.8 +/- 0.5 ml/kg) for 120 or 180 min (series 3). High Vt produced progressive lung injury with a decrease in respiratory system compliance, increase in protein concentration in lung lavage fluid, and lung pathology showing hyaline membrane formation. High-Vt ventilation was associated with increased TNF-alpha in lung lavage fluid at the early stage of injury (series 2) but not the later stage (series 1). In contrast, lavage fluid macrophage inflammatory protein-2 (MIP-2) was increased in all high-Vt animals. Lavage fluid from high-Vt animals contained bioactive TNF-alpha by WEHI bioassay. Low-Vt ventilation induced minimal changes in physiology and pathology with negligible TNF-alpha and MIP-2 proteins and TNF-alpha bioactivity. These results demonstrate that high-Vt ventilation in the absence of underlying injury induces intrapulmonary TNF-alpha and MIP-2 expression in mice. The apparently transient nature of TNF-alpha upregulation may help explain previous controversy regarding the involvement of cytokines in ventilator-induced lung injury.     

Is there a morning-to-evening difference in the acute IL-6 and cortisol responses to resistance exercise?

Exercise training is known to induce a molecular adaptation process involving inflammatory responses. However any time-of-day effect of exercise on inflammatory responses remains unknown. The aim of the present study was to investigate whether acute bouts of intense exercise performed at different times of the day would affect the release Interleukin-6 (IL-6), one of the most abundant cytokines in mammalian endocrine response to exercise. Cortisol levels were measured as a confirmation of correct timing of exercise and to determine any impact it may have on the cytokine release. Twelve healthy male participants carried out 30 min of intense exercise (3 sets of 8-12 repetitions for 4 resistance exercises at 70% of 1RM) in morning (08:15-09:00 h), and evening (18:15-19:00 h) sessions. An 8h fasting period was required before each exercise session. Blood samples were taken immediately pre and post each exercise sessions to determine IL-6 and cortisol levels. Our data show that whilst the training group showed no post-exercise changes in serum_IL-6 levels (P>0.05), the control group on the other hand showed significant time-of-day modifications in serum_IL-6 levels (P=0.008). Moreover, a significant interaction between intervention phase (pre-post training, AM vs. PM) and group (Exercise vs. Control) is evidenced in terms of serum_IL-6 levels (P=0.014). This interaction however was nullified when the between group differences at baseline were partialled out in a covariate analysis (P>0.05). We also found that the main effect of experimental phase on Cortisol was present in both the trained (P=0.004) and control groups (p<0.001) with no significant interaction (P>0.05). Based on the current data, we would propose that exercise and/or time-of-day would not interfere with clinical endocrine profiling of IL-6 in a population.     

Cytokine gene polymorphisms as potential risk and protective factors in renal cell carcinoma

Serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels in the serum of 34 patients with head and neck cancer (HNC) undergoing locoregional radiotherapy (RT) were examined. The aim of the RT was definitive in 19 and postoperative adjuvant in 15 patients. Serum TNF-alpha and IL-6 levels were recorded before RT and after the completion of the fifth week of RT. The mean TNF-alpha levels before and after RT were 28.26 +/- 2.87 and 83.03 +/- 7.47, and the mean IL-6 levels were 61.56 +/- 14.32 and 122.45 +/- 30.66, respectively. The statistical analysis yielded a significant rise in TNF-alpha levels with RT in all patients (p < 0.0001) and also in IL-6 levels in patients treated with postoperative adjuvant RT (p = 0.001). Irradiation is likely to cause an acute phase response, and the cytokines studied may be used to monitor this clinically important response in further trials.     

Time course of proteolytic, cytokine, and myostatin gene expression after acute exercise in human skeletal muscle.

The aim of this study was to examine the time course induction of select proteolytic [muscle ring finger-1 (MuRF-1), atrogin-1, forkhead box 3A (FOXO3A), calpain-1, calpain-2], myostatin, and cytokine (IL -6, -8, -15, and TNF-alpha) mRNA after an acute bout of resistance (RE) or run (RUN) exercise. Six experienced RE (25 +/- 4 yr, 74 +/- 14 kg, 1.71 +/- 0.11 m) and RUN (25 +/- 4 yr, 72 +/- 5 kg, 1.81 +/- 0.07 m) subjects had muscle biopsies from the vastus lateralis (RE) or gastrocnemius (RUN) before, immediately after, and 1, 2, 4, 8, 12, and 24 h postexercise. RE increased (P < 0.05) mRNA expression of MuRF-1 early (3.5-fold, 1-4 h), followed by a decrease in atrogin-1 (3.3-fold) and FOXO3A (1.7-fold) 8-12 h postexercise. Myostatin mRNA decreased (6.3-fold; P < 0.05) from 1 to 24 h postexercise, whereas IL-6, IL-8, and TNF-alpha mRNA were elevated 2-12 h. RUN increased (P < 0.05) MuRF-1 (3.6-fold), atrogin-1 (1.6-fold), and FOXO3A (1.9-fold) 1-4 h postexercise. Myostatin was suppressed (3.6-fold; P < 0.05) 8-12 h post-RUN. The cytokines exhibited a biphasic response, with immediate elevation (P < 0.05) of IL-6, IL-8, and TNF-alpha, followed by a second elevation (P < 0.05) 2-24 h postexercise. In general, the timing of the gene induction indicated early elevation of proteolytic genes, followed by prolonged elevation of cytokines and suppression of myostatin. These data provide basic information for the timing of human muscle biopsy samples for gene expression studies involving exercise. Furthermore, this information suggests a greater induction of proteolytic genes following RUN compared with RE.     

Modifications of serum glycoproteins the days following a prolonged physical exercise and the influence of physical training.

Eight male subjects (mean age 24.1 +/- 2.6 years) performed at intervals of 2 weeks successively a 3 h and two 2 h runs of different running speed. The days following the running there were moderate elevations of C-reactive protein, haptoglobin, alpha-1-acid glycoprotein, coeruloplasmin, transferrin, alpha-1-antitrypsin and plasminogen. There were small or no changes of albumin, alpha-2-macroglobulin and hemopexin. The elevations of the "acute phase reactants" were examined in three male subjects following a 2 h run before and after an endurance training period of 9 weeks. This demonstrated a decreased acute phase response after training as illustrated by the changes of C-reactive protein, haptoglobin and alpha-1-acid glycoprotein in spite of higher posttraining running speeds. Well-trained athletes have elevated levels of the serum protease inhibitors alpha-1-antitrypsin, alpha-2-macroglobulin and C1-inhibitor. These antiproteolytic glycoproteins might limit exercise-induced inflammatory reactions.     

Adenosine deaminase enzyme activity is increased and negatively correlates with catalase,superoxide dismutase and glutathione peroxidase in patients with Behçet's disease: original contributions/clinical and laboratory investigations

AIM: Behçet''s disease (BD) is an inflammatory vasculitis with immunologic, endothelial and neutrophil alterations. Adenosine deaminase (AD) is a marker of T-cell activation and is related to the production of reactive oxygen species by neutrophils with the production of NO(*), O(2)(*-), H(2)O(2) and OH(*). We reported increased tumour necrosis factor-alpha, soluble interleukin-2 receptor, interleukin-6, interleukin-8 and NO(*) in active BD. As there is a relation between cytokines, T cells and oxidative stress in inflammatory diseases, this study further evaluated: (1) plasma AD activity and its correlation with acute phase reactants; (2) thiobarbituric acid-reactive substances (TBARS) as an indicator for lipid peroxidation; and (3) antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase in patients with BD. The effect of disease activity and correlations between the measured parameters were explored. METHODS: A total of 35 active (n=17) or inactive (n=18) patients with BD (16 men, 19 women) satisfying International Study Group criteria, and 20 age-matched and sex-matched controls (nine men, 11 women) were included in this cross-sectional case-control study. AD and TBARS were measured in plasma, catalase in red blood cells (RBC), and SOD and GSHPx in both plasma and RBC in both groups. Acute phase reactants (alpha(1)-antitrypsin, alpha(2)-macroglobulin, neutrophils, erythrocyte sedimentation rate) were used to classify patients as active or inactive. RESULTS: Plasma AD (mean+/-standard error of the mean, 36.1+/-0.7 U/l) and TBARS (4.2+/-0.1 nmol/ml) levels were significantly (for each, p<0.001) higher in BD than in controls (24.1+/-0.8 U/l and 1.6+/-0.1 nmol/ml, respectively). RBC catalase activity was significantly (p<0.001) lower in BD than in controls (120.9+/-3.8 versus 160.3+/-4.1 k/g haemoglobin). SOD and GSHPx activities were significantly lower in both plasma and erythrocytes of patients with BD than in controls (plasma SOD, 442.4+/-8.6 versus 636.4+/-9.2 U/ml, p<0.001; RBC SOD, 3719.2+/-66.0 versus 4849.7+/-49.0 U/g haemoglobin, p<0.001; plasma GSHPx, 73.1+/-1.5 versus 90.6+/-2.9 U/ml, p<0.001; RBC GSHPx, 600.7+/-8.0 versus 670.6+/-10.1 U/g haemoglobin, p<0.001). Active BD patients had significantly lower antioxidant enzymes (except RBC catalase) and higher AD and TBARS levels than inactive subjects (for each, p<0.01). When considering all BD patients, a significant positive correlation was present between AD and TBARS (p<0.001) whereas both AD and TBARS were negatively correlated with antioxidant enzymes (for each, p<0.05). CONCLUSIONS: AD and lipid peroxidation are increased and associated with defective antioxidants in BD, suggesting interactions between activated T cells and neutrophil hyperfunction. Measures of pro-oxidative stress and antioxidative defence with AD activity as an indicator of T-cell activation can be considered as significant supportive diagnostic indicators, especially in active disease. In addition, strengthening the antioxidant defence may contribute to treatment modalities.     

Exercise-induced prostacyclin release positively correlates with VO(2max) in young healthy men

In this study we have evaluated the effect of maximal incremental cycling exercise (IE) on the systemic release of prostacyclin (PGI(2)), assessed as plasma 6-keto-PGF(1alpha) concentration in young healthy men. Eleven physically active - untrained men (mean +/- S.D.) aged 22.7 +/- 2.1 years; body mass 76.3 +/- 9.1 kg; BMI 23.30 +/- 2.18 kg . m(-2); maximal oxygen uptake (VO(2max)) 46.5 +/- 3.9 ml . kg(-1) . min(-1), performed an IE test until exhaustion. Plasma concentrations of 6-keto-PGF(1alpha), lactate, and cytokines were measured in venous blood samples taken prior to the exercise and at the exhaustion. The net exercise-induced increase in 6-keto-PGF(1alpha) concentration, expressed as the difference between the end-exercise minus pre-exercise concentration positively correlated with VO(2max) (r=0.78, p=0.004) as well as with the net VO(2) increase at exhaustion (r=0.81, p=0.003), but not with other respiratory, cardiac, metabolic or inflammatory parameters of the exercise (minute ventilation, heart rate, plasma lactate, IL-6 or TNF-alpha concentrations). The exercise-induced increase in 6-keto-PGF(1alpha) concentration?? was significantly higher (p=0.008) in a group of subjects (n=5) with the highest VO(2max) when compared to the group of subjects with the lowest VO(2max), in which no increase in 6-keto-PGF(1alpha) concentration was found. In conclusion, we demonstrated, to our knowledge for the first time, that exercise-induced release of PGI(2) in young healthy men correlates with VO(2max), suggesting that vascular capacity to release PGI(2) in response to physical exercise represents an important factor characterizing exercise tolerance. Moreover, we postulate that the impairment of exercise-induced release of PGI(2) leads to the increased cardiovascular hazard of vigorous exercise.     

Outer membrane vesicles from Neisseria meningitidis: effects on cytokine production in human whole blood

The Norwegian group B meningococcal outer membrane vesicle (OMV) vaccine consists of outer membrane proteins (OMPs) as main antigens with significant amounts of lipopolysaccharide (LPS; 5-9% relative to protein). We have studied the ability of this OMV vaccine preparation to induce secretion of pro-inflammatory cytokines, tumour necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), interleukin 6 (IL-6), interleukin 8 (IL-8) and anti-inflammatory cytokines, interleukin 4 (IL-4), interleukin 10 (IL-10) and interleukin 13 (IL-13) in a human whole blood model. Plasma levels of TNF-alpha, IL-1beta, IL-6 and IL-8 were massively increased; mean peak levels of TNF-alpha 44 696+/-7764, IL-1beta 38 043+/-5411, IL-6 10 057+/-1619 and IL-8 30 449+/-5397 pg/ml were obtained with an OMV-LPS concentration of 1 microg/ml; corresponding levels in control plasmas were below the detection limit of the assay. Mean maximal level of IL-10 (2540+/-144 pg/ml) was obtained at OMV-LPS concentration of 10 microg/ml, after 24 h; while the level in control plasma was below detection limit. OMV-LPS did not induce release of IL-4 and IL-13 in doses from 0.001-10 microg/ml. The present results show that OMVs from meningococci have potent pro-inflammatory properties and are likely to contribute to the observed local and systemic inflammatory effects.     

Creatine supplementation reduces plasma levels of pro-inflammatory cytokines and PGE<Subscript>2</Subscript> after a half-ironman competition

OBJECTIVE: The effect of creatine supplementation upon plasma levels of pro-inflammatory cytokines: Interleukin (IL) 1 beta and IL-6, Tumor Necrosis Factor alpha (TNFalpha), and Interferon alpha (INF alpha) and Prostaglandin E(2) (PGE(2)) after a half-ironman competition were investigated. METHODS: Eleven triathletes, each with at least three years experience of participation in this sport were randomly divided between the control and experimental groups. During 5 days prior to competition, the control group (n = 6) was supplemented with carbohydrate (20 g x d(-1)) whereas the experimental group (n = 5) received creatine (20 g x d(-1)) in a double-blind trial. Blood samples were collected 48 h before and 24 and 48 h after competition and were used for the measurement of cytokines and PGE(2). RESULTS: Forty-eight hours prior to competition there was no difference between groups in the plasma concentrations (pg x ml(-1), mean +/- SEM) of IL-6 (7.08 +/- 0.63), TNFalpha (76.50 +/- 5.60), INF alpha (18.32 +/- 1.20), IL-1 beta (23.42 +/- 5.52), and PGE(2) (39.71 +/- 3.8). Twenty-four and 48 h after competition plasma levels of TNFalpha, INF alpha, IL-1 beta and PGE(2) were significantly increased (P < 0.05) in both groups. However, the increases in these were markedly reduced following creatine supplementation. An increase in plasma IL-6 was observed only after 24 h and, in this case, there was no difference between the two groups. CONCLUSION: Creatine supplementation before a long distance triathlon competition may reduce the inflammatory response induced by this form of strenuous of exercise.     

Docosahexanoic acid diet supplementation attenuates the peripheral mononuclear cell inflammatory response to exercise following LPS activation

Exercise induces changes in circulating pro- and anti-inflammatory cytokines. The aim was to investigate the effect of docosahexaenoic acid (DHA) diet supplementation on the plasma cytokine levels and on the peripheral mononuclear (PBMCs) cells cytokine production after a training season or an acute bout of exercise. Fifteen male soccer players were randomly assigned to a placebo or an experimental group. The experimental group consumed an almond-based beverage enriched with DHA, whereas the placebo group consumed the same beverage without DHA. Three blood samples were taken: in basal conditions at the beginning of the nutritional intervention and after eight weeks of training season in basal and post-exercise conditions. The DHA content increased in erythrocytes after 8 weeks of training and supplementation. Neither diet supplementation with DHA nor training season altered the basal plasma cytokines and growth factors. Only acute exercise significantly increased plasma IL6 in experimental and placebo groups. Lipopolysaccharide (LPS) activation induced the inflammatory response in PBMCs, with a significant production rate of TNFα, IL6 and IL8 mainly after acute exercise. DHA supplementation significantly reduced the rate of TNFα and IL6 production by stimulated PBMCs. Acute exercise increased the Toll-like receptor 4 (TLR4) protein levels in PBMCs, although the increase was only statistically significant in the placebo group. In conclusion, a training season does not induce significant changes in the circulating cytokine profile in well-trained soccer players. Exercise increases the PBMCs cell capabilities to produce cytokines after TLR4 stimulation with LPS and this rate of cytokine production is attenuated by diet DHA supplementation.     

Exercise enhances myocardial ischemic tolerance via an opioid receptor-dependent mechanism

Exercise increases serum opioid levels and improves cardiovascular health. Here we tested the hypothesis that opioids contribute to the acute cardioprotective effects of exercise using a rat model of exercise-induced cardioprotection. For the standard protocol, rats were randomized to 4 days of treadmill training and 1 day of vigorous exercise (day 5), or to a sham exercise control group. On day 6, animals were killed, and global myocardial ischemic tolerance was assessed on a modified Langendorff apparatus. Twenty minutes of ischemia followed by 3 h of reperfusion resulted in a mean infarct size of 42 +/- 4% in hearts from sham exercise controls and 21 +/- 3% (P < 0.001) in the exercised group. The cardioprotective effects of exercise were gone by 5 days after the final exercise period. To determine the role of opioid receptors in exercise-induced cardioprotection, rats were exercised according to the standard protocol; however, just before exercise on days 4 and 5, rats were injected subcutaneously with 10 mg/kg of the opioid receptor antagonist naltrexone. Similar injections were performed in the sham exercise control group. Naltrexone had no significant effect on baseline myocardial ischemic tolerance in controls (infarct size 43 +/- 4%). In contrast, naltrexone treatment completely blocked the cardioprotective effect of exercise (infarct size 40 +/- 5%). Exercise was also associated with an early increase in myocardial mRNA levels for several opioid system genes and with sustained changes in a number of genes that regulate inflammation and apoptosis. These findings demonstrate that the acute cardioprotective effects of exercise are mediated, at least in part, through opioid receptor-dependent mechanisms that may include changes in gene expression.     

Circulating plasma VEGF response to exercise in sedentary and endurance-trained men.

The skeletal muscle capillary supply is an important determinant of maximum exercise capacity, and it is well known that endurance exercise training increases the muscle capillary supply. The muscle capillary supply and exercise-induced angiogenesis are regulated in part by vascular endothelial growth factor (VEGF). VEGF is produced by skeletal muscle cells and can be secreted into the circulation. We investigated whether there are differences in circulating plasma VEGF between sedentary individuals (Sed) and well-trained endurance athletes (ET) at rest or in response to acute exercise. Eight ET men (maximal oxygen consumption: 63.8 +/- 2.3 ml x kg(-1) x min(-1); maximum power output: 409.4 +/- 13.3 W) and eight Sed men (maximal oxygen consumption: 36.3 +/- 2.1 ml x kg(-1) x min(-1); maximum power output: 234.4 +/- 13.3 W) exercised for 1 h at 50% of maximum power output. Antecubital vein plasma was collected at rest and at 0, 2, and 4 h postexercise. Plasma VEGF was measured by ELISA analysis. Acute exercise significantly increased VEGF at 0 and 2 h postexercise in ET subjects but did not increase VEGF at any time point in Sed individuals. There was no difference in VEGF between ET and Sed subjects at any time point. When individual peak postexercise VEGF was analyzed, exercise did increase VEGF independent of training status. In conclusion, exercise can increase plasma VEGF in both ET athletes and Sed men; however, there is considerable variation in the individual time of the peak VEGF response.     

Serum IL-18 is increased at early postburn period in moderately burned patients

A severe systemic inflammatory response is usually seen after burn injury. IL-18 enhances the Th1 immune responses in bacterial andviral infections. In order to evaluate the IL-18 serum levels as well as IL-6 and TNF-alpha at the 48th hour postburn, serial serum samples of 8 burned patients were analyzed. 8 moderately burned patients were included into the study. Serum samples were taken at admission at the 48th hour of postburn. IL-6, IL-18, and TNF-alpha serum levels were analyzed. Total mean burned surface area (TBSA) was 24.6 +/- 5.7% and mean BMI (body mass index) was 24.5 +/- 3.4. The patients' age ranged from 17 to 38 (mean 26.3 +/- 7.4) years. An increase in sera IL-6, IL-18, and TNF-alpha was detected at the 48th hour postburn (P < .0001). All patients survived. A marked increase in serum levels of IL-18 as well as the other cytokines evaluated was observed in the moderately burned patients. These three parameters were highly correlated with each other (r > 0.9 and P < .001). This is the first study that shows an increase in serum IL-18 levels at the early postburn period.