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Morphological changes of myofibers after eccentric exercises. A, The control group. B, The 24-hour group. Swollen myofibers (arrowheads) and disrupted myofibers (arrows) are detected. C, The 3-day group. Many myofibers are swollen or disrupted. Small cells (arrowheads) are detected among myofibers. Those cells are probably inflammatory cells and proliferating satellite cells. D, The 7-day group. Myofibers with central nuclei (arrowheads) are detected, which indicates the regeneration of muscle tissue. Hematoxylin and eosin staining. Original magnification is ×200.
Source publication
Interleukin (IL)-6 is locally produced in skeletal muscles and shows a remarkable increase in plasma after eccentric exercises.
To elucidate the cell types in the muscles responsible for IL-6 production after eccentric exercises.
Controlled laboratory study.
An eccentric contraction model was made using electrical stimulation. The authors investiga...
Contexts in source publication
Context 1
... group, some swollen myofibers appeared with a rounded, large, and lightly stained cytoplasm by eosin. The diameter of those swollen myofiber was about 60 µm. In the 12-hour group, the num- ber of such cells was increased. In the 24-hour group, focal myofiber disruptions were "moth-eaten" shaped, and many inflammatory cells were found around them (Fig. 1B). In the 3-day group, the myofiber disruptions were more prominent. Small cells were accumulated near the disrupt- ed myofibers (Fig. 1C). Those small cells include inflamma- tory cells and proliferating satellite cells positively stained for Pax-7 (Fig. 2). In the 7-day group, myofibers with cen- tral nuclei were observed (Fig. 1D). In ...
Context 2
... was about 60 µm. In the 12-hour group, the num- ber of such cells was increased. In the 24-hour group, focal myofiber disruptions were "moth-eaten" shaped, and many inflammatory cells were found around them (Fig. 1B). In the 3-day group, the myofiber disruptions were more prominent. Small cells were accumulated near the disrupt- ed myofibers (Fig. 1C). Those small cells include inflamma- tory cells and proliferating satellite cells positively stained for Pax-7 (Fig. 2). In the 7-day group, myofibers with cen- tral nuclei were observed (Fig. 1D). In the 14-and 21-day groups, no disrupted myofibers or inflammatory cells were ...
Context 3
... around them (Fig. 1B). In the 3-day group, the myofiber disruptions were more prominent. Small cells were accumulated near the disrupt- ed myofibers (Fig. 1C). Those small cells include inflamma- tory cells and proliferating satellite cells positively stained for Pax-7 (Fig. 2). In the 7-day group, myofibers with cen- tral nuclei were observed (Fig. 1D). In the 14-and 21-day groups, no disrupted myofibers or inflammatory cells were ...
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Citations
... 63 Considering that IL-6 is released from inflammatory cells and the endothelium during an injury or infection, it is assumed that it exerts a proinflammatory function, in addition of being related to delayed-onset muscle soreness. 64 It is thought that the reduction in muscle blood flow caused by CWI prevents the clearance of IL-6 produced by the muscle. Therefore, during long immersions, this process can result in persistence of IL-6 in the bloodstream for a longer period, 61 hindering a satisfactory analgesic effect of CWI. ...
Objective:
Our objective was to determine the efficacy of cold-water immersion (CWI) on the management of muscle soreness to identify the impact of immersion time, water temperature, CWI protocol, and type of exercise on this outcome.
Design:
Intervention systematic review and meta-analysis.
Setting:
MEDLINE/PubMed, Embase, Central, and SPORTDiscus databases were searched from their earliest record to July 30, 2020. Only randomized controlled trials that assessed muscle soreness comparing CWI and control were included. Studies were pooled in different subgroups regarding the used protocol: water temperature (severe or moderate cold), immersion time (short, medium, or longer time), CWI protocol (intermittent or continuous application), and type of exercise (endurance or resistance exercise). Data were pooled in a meta-analysis and described as weighted mean difference (95% confidence interval, P < 0.05).
Participants:
Athletes and nonathletes.
Interventions:
Cold-water immersion and control condition.
Main outcome measures:
Muscle soreness.
Results:
Forty-four studies were included. For immediate effects, CWI was superior to control regardless of water temperature and protocol, and for short and medium immersion times and endurance exercises. For delayed effects, CWI was superior to control in all subgroups except longer immersions time.
Conclusions:
This study suggests that CWI is better than control for the management of muscle soreness and water temperature and CWI protocol do not influence this result, but only short and medium immersions times presented positive effects. Aiming immediate effects, the best results suggest CWI application only after endurance exercises, while delayed effect CWI was superior both after endurance and resistance exercises.
... They failed to detect any changes in the amount of IL-6 protein in muscles after exercise. However, Tomiya et al. (2004) found that the highest ratio of IL-6 expression in myofibers appeared 12 h after eccentric exercise and decreased to normal levels from 7 to 21 days; this suggested that IL-6 might be related to both muscle damage and muscle regeneration. The discrepancy of the two studies may be accounted for 1 3 by the different exercise protocols employed (eccentric cycling exercise versus electric stimulated eccentric contraction), indicating that IL-6 expression might be diversified according to the eccentric exercise model. ...
... In our present study, IL-6 had a rapid increased transcriptional response at 6 h after eccentric exercise, and we found that both myocytes and infiltrating inflammatory cells were the cellular sources of IL-6 production, as verified by in situ hybridization staining (Fig. 5: IL-6, 6 h). This is consistent with the results of Tomiya et al. (2004) and Safran et al. (1989), suggesting that infiltrating inflammatory cells induced IL-6 in damaged human muscles (Ostrowski et al. 1998) and that the source may be mainly M1 macrophages (Kharraz et al. 2013). In our previous work, we found that the earliest M1 macrophage invasion appeared at 6 h after eccentric exercise (Zuo et al. 2018), which coincided with the time and space that IL-6 mRNA showed a positive signal in the present study ( Fig. 5: IL-6, 6 h). ...
... Previous findings indicate that, during the recovery and regeneration processes, IL-6 derived from myofiber and inflammatory cells can facilitate satellite cell activation and induce expression of myogenic regulating factors (e.g., MyoD and Myf5) (Tidball and Villalta 2010). Different from the result by Tomiya et al. (2004) that IL-6 decreased to normal from 7 to 21 days after eccentric exercise at the protein level, in our present study, we found high levels of IL-6 protein located in the cytoplasm of muscle fibers up to 2 weeks post-exercise ( Fig. 6: IL-6, 2 weeks; Fig. 7: IL-6) and at the gene level IL-6 was mainly expressed by myonuclear cells at 2 weeks after exercise (Fig. 5: IL-6, 2 weeks). Our results indicate that in addition to being involved in enhanced protein degradation during muscle damage, the muscle-derived IL-6 might support subsequent muscle regeneration in the late phase by inducing the proliferation of satellite cells to form myotubes (Bruunsgaard et al. 1997). ...
Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) are well-known cytokines with pro-inflammatory capabilities, and have been shown to be involved in adaptation to exercise as multifaceted myokines. However, the precise role of IL-6 and TNF-α during exercise-induced skeletal muscle injury and subsequent repair processes is not fully understood. In this study, IL-6 and TNF-α were examined in soleus muscles at the gene and protein levels using in situ hybridization and immunohistochemical staining, respectively, and serum levels of IL-6 and TNF-α were determined before and after a 90-min downhill running session in rats. There were no changes in serum levels of IL-6 and TNF-α after exercise, but IL-6 and TNF-α mRNA increased and maintained high expression in muscles for 1–2 weeks after exercise. IL-6 and TNF-a mRNAs were identified in both the cytoplasm and the nuclei of myocytes, as well as in invading inflammatory cells. IL-6 and TNF-α protein mainly distributed in cytoplasm unevenly and had a prolonged expression until 2 weeks after eccentric exercise. Our results demonstrate that there is increased IL-6 and TNF-α expression in skeletal muscle that is induced by eccentric exercise and that the high expression of IL-6 and TNF-α in the long-term phase after eccentric exercise may be more involved in the subsequent recovery of damaged muscle.
... Unlike the pro-inflammatory cytokines, exercise-induced alterations in the antiinflammatory cytokines are less identified. Few available studies have used RT as a muscle-damaging exercise protocol to induce inflammation (12,32,33). In addition to this, most of the data regarding the IL-4 and IL-13 is derived from protein/mRNA of these cytokines in response to exercise training (34) and there is a lack of evidence on the circulating alterations of these cytokines in response to exercise training. ...
Objective: The overweight-related health problems among adolescents are obvious. Resistance training is recognized as a safe and efficacious exercise modality to have health-promoting effects in overweight adolescents. This study aimed to assess the efficacy of circuit resistance training (CRT) in improving inflammatory status, insulin resistance and body composition in overweight male adolescents.
Materials and Methods: Twenty overweight adolescent boys (aged: 18.5 (±1), weight: 81.1 (±4.5), body mass index: 27.7 (±0.7)) completed this study. The participants were randomly and equally divided into two groups of control (CG; n=10) and circuit resistance training (CRT; n=10). The CG did their daily routine activities and the CRT group performed its training protocol 3 days a week for 6 weeks. Body composition components and serum variables were measured a day before and after the study. Insulin resistance index was measured by HOMA-IR.
Results: The subjects in the CG showed significantly increased changes compared with pre-training values. Moreover, significant changes were found fort the changes of BW (P-value= 0.005), BMI (P-value= 0.001) and BF% (P-value= 0.003) between groups.
Conclusion: This study suggested that although six weeks of CRT failed to induce meaningful anti-inflammatory cytokine responses, and to improve body composition and HOMA-IR in overweight adolescent boys, but had protective effects on inflammatory status, HOMA-IR and body composition and prevented them from being deteriorated.
... Bu etkiler, uydu hücre aktivitesinin artması ve miyonükleer çoğalma olarak ifade edilmektedir. 80,84,85 İskelet kasının büyümesinde potansiyel role sahip olan bir diğer sitokin ise IL-15' dir. Direnç antrenmanını takiben artan IL-15 cevabı inflamasyon ve oksidatif stresin (veya her ikisi) bir cevabı olarak kas fibrilinde meydana gelen mikrotravmalar yoluyla sekrete olmaktadır. ...
... Histological samples of muscles are often analyzed in animal studies that involved muscular damage. The standard hematoxylin-eosin staining is most common, and allows the visualization of swollen 34 and necrotic fibers 35,36 , the infiltration of immune cells 36,37 and the presence of regenerative fibers 34 . Another easy possibility to detect the damaged fibers is the staining with a secondary antibody for immunoglobulins (IgG) 38 . ...
... Histological samples of muscles are often analyzed in animal studies that involved muscular damage. The standard hematoxylin-eosin staining is most common, and allows the visualization of swollen 34 and necrotic fibers 35,36 , the infiltration of immune cells 36,37 and the presence of regenerative fibers 34 . Another easy possibility to detect the damaged fibers is the staining with a secondary antibody for immunoglobulins (IgG) 38 . ...
... The degeneration of the quadriceps at 48h after the damaging exercise involved the presence of necrotic fibers, neutrophils and macrophages and the increase of the CK, like shown previously in the literature 35,88 . At 72h, it was expected to see more foci of infiltrated cells and and even a higher fold change of the CK 15,34,89 . Instead, only hypereosinophilic round fibers and swollen fibers were observed ( Figure 24). ...
In the last years, the photobiomodulation (PBM) has been proposed as a treatment to speed up the recovery of muscles which underwent a damaging exercise. Several studies report the effectiveness of the PBM in improving the status of injured skeletal muscles, however, little is known about the mechanisms of cellular signaling behind it. The main aim of the present work, is to evaluate the effect of the infra-/red light on exercised muscles during the inflammation, which is a crucial phase that affects the regeneration, and therefore the functional recovery of the muscles. The effect of the infra-/red light was compared to the application of another treatment, the cryotherapy, which is a common post-exercise practice. Preliminary studies on a cell line of muscular cells (C2C12) were carried on in order to confirm the main findings reported in literature and to support the following in vivo study. The in vivo study consisted in the application of the light therapy and the cryotherapy to the lower limbs of 10 weeks old CD-1 male mice, after performing a damaging exercise. Qualitative and quantitative comparisons were done on the concentration of plasma parameters and on the morphology of histological samples. A comprehensive gene expression profiling and comparison among the experimental groups was performed in order to detect marker genes involved in process of inflammation, repair and regeneration, and identify signaling pathways regulated by the different treatments. Independently from the type of recovery (with or without therapy), the quadriceps displayed signs of damage at 48h after exercise: increase of CK levels; necrosis of fibers detected in the histology; upregulation of genes coding for costameres, membrane repair proteins, and MFRs. Instead, the gene expression of the exercised and irradiated quadriceps revealed the upregulation of pathways related to both pro-inflammation and anti-inflammation phase. Moreover, chemokines and markers for different phenotypes of macrophages and T cells were significantly upregulated only by the infra-/red light. These results suggested that the signaling cascades related to the regeneration phase had begun earlier in the PMB group. The main finding of this project is that the immune system was stimulated by the infra-/red therapy while the cryotherapy mitigated the structural deterioration and inflammation. Which of the therapies is the best one for the recovery post-exercise, is still an open issue. It is a matter of clarifying if the light therapy speeds up the inflammatory process in advance of the regeneration or prolonging it, and if the cryotherapy protects from the damage or suppresses the inflammation delaying regeneration process.
... Corroborando o estudo de Tomiya et al. 21 o presente estudo mostrou que o treino resistido excêntrico, foi mais eficiente no ganho de força quando comparados ao isométrico ou concêntrico, nas respectivas velocidades (30º/s e 120º/s) testadas. ...
Introduction:
Eccentric training and jump tests are widely used to recover and measure deficits in knee strength and functionality after anterior cruciate ligament (ACL) reconstruction.
Objective:
To correlate knee extension and flexion torque generated by eccentric isokinetic training, with functional jump tests in subjects with reconstructed ACL.
Method:
Sixteen men with unilateral ACL reconstruction were assessed before and after 12 weeks of eccentric isokinetic training of knee flexors and extensors (3×10 MVC, 2x/week) at 30°/s for extension and flexion torque (isometric; concentric and eccentric at 30 and 120°/s) and functional jump tests (single, triple, cross and figure of 8). Inter- and intra-limb pre- and post-training mean peak torque (MPT), distance and jump test times were compared along with the correlations between these variables, considering P<0.05.
Results:
The affected limb (AL) showed significant gain of extension and flexion torque (P<0.01) in the different test categories and velocities evaluated. In the non-affected limb (NAL), this only occurred in the eccentric category (30 and 120°/s), in the extension (P<0.01) and flexion (P<0.05 and P<0.01) torques, respectively. In the jumps, there was an increase in distance (single and triple; P<0.05) and a decrease in time (crossed and figure of 8; P<0.01), however, MPT x Jump correlations were weak (r<0.3) in the pre and post-training period in both limbs.
Conclusion:
Despite the gain in knee extension and flexion torque and jumping performance, the expected correlation was not satisfactory, suggesting that knee functionality involves other variables inherent to motor control. Level of Evidence IV; Type of study: Case series.
... One of the iron-containing proteins is ferritin performing the function of cellular iron depot, as well as the detoxification function as it reduces the content of catalytically active iron [29]. Ferritin molecule consists of 2 types of subunits, L and H; the latter subunits display a ferrooxidase activity, oxidizing Fe 2+ to Fe 3+ for depositing [30]. Taking into account that the affinity of H ferritin subunits exceeds the concentration of free iron present in the cell, it has been supposed that there is a specific mechanism necessary for iron delivery to the ferritin molecule. ...
Intense physical activity has a significant effect on iron metabolism in the human organism. This paper is a review of world literature data focused on the mechanisms of iron metabolism regulation in the human organism, as well as the influence of intense exercise on these regulatory mechanisms. We have discussed the mechanisms of iron absorption and transport and the regulation of these processes under normal conditions. It has been found that intense exercise is accompanied by increased production of interleukin-6, a positive regulator of hepcidin production. Hepcidin, in turn, has an inhibitory effect on the expression of divalent metal transporter 1 and ferroportin, finally leading to both decreased iron absorption and iron sequestration in cells. All of the mentioned stages of iron deficiency development may be promising targets for correction of iron balance and working ability in patients exposed to intense physical activity.
... Studies have shown that myocytes and other cells can release IL-1β, IL-6, and TNF-α when skeletal muscle is damaged. [30][31][32][33][34][35] The role of IL-6 in exercise-induced skeletal muscle injury was suggested in studies of eccentric exercise (a common model of exercise-induced skeletal muscle damage). [31] Tomiya et al. [32] produced eccentric contraction of muscle through electrical stimulation. ...
... [30][31][32][33][34][35] The role of IL-6 in exercise-induced skeletal muscle injury was suggested in studies of eccentric exercise (a common model of exercise-induced skeletal muscle damage). [31] Tomiya et al. [32] produced eccentric contraction of muscle through electrical stimulation. IL-6 was detected in the muscle cytoplasm 12 h after eccentric exercise, and it was also detected in inflammatory cells and proliferating satellite cells, [33] suggesting that the cytokine is associated with the inflammatory responses in eccentric exercise-induced muscle damage. ...
Background: Dandelion is commonly used in traditional Chinese medicine with several active compounds found in extracts. It has a variety of pharmacological effects, such as a reduction in swelling and inflammation, and detoxification. The mechanism by which dandelion extract inhibits the inflammatory response in skeletal muscle cells remains unknown; therefore, the aim of this study was to investigate the effects of dandelion extract root on the proliferation of skeletal muscle cells and the alleviation of lipopolysaccharide (LPS)-induced inflammatory response in vitro.
Methods: Rat skeletal muscle cells were isolated from Sprague-Dawley rat and cultured in vitro which were cultured in basal medium, or medium containing LPS or dandelion extract. Cell counting kit-8 (CCK-8) was employed to measure cell proliferation; meanwhile, the optimal concentration of dandelion extract and treatment time were selected. Crystal violet staining was used to detect the proliferation of muscle cells. Western blotting analysis was used to detect the levels of inflammatory factors, myogenic factor, and p-AKT protein expression.
Results: The optimal concentration and treatment time of dandelion extract for the following study were 5 mg/ml and 4 days, respectively. Dandelion extract was found to increase proliferation of rat skeletal muscle cells (t = 3.145, P < 0.05), with the highest effect observed at 5 mg/ml. LPS was found to decrease proliferation of skeletal muscle cells (t = −131.959, P < 0.001), and dandelion extract could against this affection (t = 19.466, P < 0.01). LPS could induce expression of inflammatory factors, including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α (IL-1β: t = 9.118, P < 0.01; IL-6: t = 4.346, P < 0.05; TNF-α: t = 15.806, P < 0.05), and dandelion extract was shown to reduce LPS-induced expression of IL-1β, IL-6 and TNF-α (IL-1β: t = −2.823, P < 0.05; IL-6: t = −3.348, P < 0.01; and TNF-α: t = −3.710, P < 0.01). Furthermore, LPS was also shown to decrease expression of myogenic factor, including myod1 and myogenin (MyoD1: t = 4.039, P < 0.05 and myogenin: t = 3.300, P < 0.01), but dandelion extract was shown to against this effect of LPS (MyoD1: t = −3.160, P < 0.05 and myogenin: t = −3.207, P < 0.01). And then, LPS was found to increase expression of p-AKT protein (p-AKT/AKT: t = 4.432, P < 0.05). Moreover, expression of p-AKT protein was found to decrease, with 5 mg/ml of dandelion extract (p-AKT/AKT: t = −3.618, P < 0.05).
Conclusions: The findings indicate that dandelion extract plays an important role in skeletal muscle cells viability regulation, promote cells proliferation by increasing level of p-AKT protein expression, and reduce LPS-induced expression of inflammatory factors, inhibiting the inflammatory response of rat skeletal muscle cells.
... Thus, this cytokine is also involved in enhanced protein degradation, proliferating satellite cells which may support muscle regeneration. [11][12][13] Once active, the satellite cells follow an ordered set of events, including proliferation, migration, and incorporation into the adult overloaded myofibers, leading to myofibers growth. 12 IL-6 typically signals through the common gp130 receptor, with the Janus kinase/signal transducer and the activator of transcription (JAK/STAT) pathway being the major intracellular mediator of their effects. ...
... Thus, this cytokine is also involved in enhanced protein degradation, proliferating satellite cells which may support muscle regeneration. [11][12][13] Once active, the satellite cells follow an ordered set of events, including proliferation, migration, and incorporation into the adult overloaded myofibers, leading to myofibers growth. 12 IL-6 typically signals through the common gp130 receptor, with the Janus kinase/signal transducer and the activator of transcription (JAK/STAT) pathway being the major intracellular mediator of their effects. ...
