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Skeletal muscle, the largest organ in the human body, has been identified as an endocrine organ that produces and releases cytokines, which are now referred to as myokines. Research has shown that skeletal muscles produce and release significant levels of interleukin-6 (IL-6) after prolonged exercise. IL-6 is a multifunctional molecule that is both pro-inflammatory and anti-inflammatory, depending on the context. It is also a myokine that is synthesised and secreted by muscles.
| Characteristics | Values |
|---|---|
| Skeletal muscle | An endocrine organ that produces and releases cytokines |
| Cytokines produced by skeletal muscle | Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-15 (IL-15) |
| IL-6 production | Increased by physical exercise, especially in proportion to the length of exercise and the amount of muscle mass engaged |
| IL-6 function | Plays a role in muscle regeneration after injury, stimulates glucose uptake, enhances insulin secretion, stimulates lipolysis, influences lipid metabolism, acts as an energy allocator |
| IL-8 function | Stimulates angiogenesis through CXCR2 receptor signaling |
| IL-15 function | Exists in two isoforms with different signaling peptide forms |
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What You'll Learn
Interleukin-6 (IL-6) is a myokine
Skeletal muscle has been identified as an endocrine organ that produces and releases cytokines, which have been named "myokines". Interleukin-6 (IL-6) is one such myokine. It is a cytokine with a wide range of biological activities, including immune regulation, hematopoiesis, inflammation, and oncogenesis. IL-6 is secreted by a variety of cells, including lymphocytes, macrophages, and smooth muscle cells. It is significantly elevated with exercise and precedes the appearance of other cytokines in the circulation.
IL-6 was discovered as a myokine due to its exponential increase in response to exercise duration and muscle mass engagement. The plasma concentration of IL-6 increases during muscular exercise, followed by the appearance of anti-inflammatory cytokines such as IL-1 receptor antagonist (IL-1ra) and IL-10. Exercise-induced IL-6 release is associated with a reduction in abdominal obesity, as it prevents obesity, stimulates lipolysis, and is released from skeletal muscle.
IL-6 has a dual role as both a pro-inflammatory and an anti-inflammatory myokine. It can activate anti-inflammatory pathways and inhibit pro-inflammatory cytokines such as TNF and IL-1. However, excessive production of IL-6 can occur in inflammatory diseases, and it has been linked to chronic inflammatory disorders such as Crohn's disease, atherosclerosis, and rheumatoid arthritis.
IL-6 also has important implications for health and disease. For example, it has been studied in the context of COVID-19, where elevated IL-6 levels can indicate severe infection and poor prognosis. Additionally, IL-6 signaling in liver cells has been shown to suppress hepatic inflammation and improve systemic insulin action.
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IL-6 is released during physical exercise
Interleukin-6 (IL-6) is a cytokine with multiple functions in different tissues and organs. It is released into the circulation during physical exercise, with levels increasing proportionally to the length of exercise and the amount of muscle mass engaged. The mode, intensity, and duration of exercise determine the magnitude of the exercise-induced increase in plasma IL-6.
IL-6 is produced and released by skeletal muscle, which has recently been identified as an endocrine organ. During exercise, IL-6 is acutely released from working muscle fibres, with increased exercise duration, intensity, and muscle glycogen depletion. This release of IL-6 during exercise is associated with upregulation of anti-inflammatory gene expression and improved insulin sensitivity.
The cytokine response to exercise differs from that of sepsis, as the cytokine response to exercise is not preceded by an increase in plasma TNF-α. Following exercise, the basal plasma IL-6 concentration may increase up to 100-fold, although less dramatic increases are more frequent. The peak IL-6 level is typically reached at the end of the exercise or shortly thereafter.
IL-6 has been shown to play a role in mediating some of the health benefits of exercise. It contributes to the regulation of glucose and lipid metabolism, induces anti-inflammatory effects, and has anabolic properties. IL-6 also plays a role in controlling tumour growth and has been shown to suppress tumour growth through epinephrine-dependent and IL-6-dependent NK cell mobilization and redistribution.
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IL-6 is a pro-inflammatory and anti-inflammatory cytokine
Skeletal muscle has been identified as an endocrine organ that produces and releases cytokines, which are now referred to as "myokines". Research has shown that exercise induces considerable changes in the immune system, and the interactions between exercise and the immune system have provided a unique opportunity to evaluate the role of underlying endocrine and cytokine mechanisms.
Interleukin-6 (IL-6) is a cytokine with pleiotropic functions in different tissues and organs. It is a multifunctional molecule that is both pro-inflammatory and anti-inflammatory, depending on the context. IL-6 is produced and released by skeletal muscle after prolonged exercise. It was discovered as a myokine because of the observation that its concentration increases up to 100-fold in the circulation during physical exercise.
IL-6 is considered pro-inflammatory because it may play a role in the pathophysiology of primary fatigue in patients with multiple sclerosis (MS). It is also one of the most important pro-inflammatory cytokines, along with IL-1 beta, TNF-alpha, and IFN-gamma. In addition, IL-6 contributes to muscle regeneration after injury, impacting satellite cells to modify their reparative functions.
On the other hand, IL-6 is considered anti-inflammatory because it enhances insulin secretion by increasing glucagon-like peptide-1 (GLP-1) secretion from L cells and alpha cells. It also stimulates lipolysis and fat oxidation in humans. Furthermore, IL-6 increases insulin-stimulated glucose disposal and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase.
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IL-6 is synthesised by fibroblasts, monocytes, macrophages, T cells, endothelial cells, adipocytes, and myoblasts
Skeletal muscle has recently been identified as an endocrine organ that produces and releases cytokines, which are now referred to as "myokines". Research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. These include interleukins such as IL-6, which is synthesised by fibroblasts, monocytes, macrophages, T cells, endothelial cells, adipocytes, and myoblasts.
IL-6 is a cytokine with pleiotropic functions in different tissues and organs. It is a pro-inflammatory cytokine that is involved in the development of chronic inflammation, antigen-specific immune responses, and the regulation of host defence mechanisms. IL-6 is also involved in multiple signalling pathways, including the classical signalling pathway, trans-signalling pathway, and the recently discovered trans-presentation.
IL-6 is produced by a variety of cells, including T cells, B cells, macrophages, neutrophils, monocytes, keratinocytes, fibroblasts, endothelial cells, epithelial cells, osteoblasts, chondrocytes, adipocytes, and mesangial cells. The expression of the IL-6 gene is driven by the inflammatory response, which is triggered by interferons (IFNs), tumour necrosis factor (TNF), IL-1, and bacterial lipopolysaccharide (LPS) and endotoxin.
IL-6 has been shown to play a role in the differentiation, activation, and proliferation of leukocytes, endothelial cells, keratinocytes, and fibroblasts. It is involved in the healing of cutaneous wounds, and dysregulation of IL-6 signalling can lead to either fibrosis or a failure to heal. IL-6 also plays a role in the differentiation of monocytes into macrophages, and it has been shown to promote the survival of myofibroblasts.
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IL-6 stimulates glucose uptake
Skeletal muscle has been identified as an endocrine organ that produces and releases cytokines, or "myokines", in response to contraction. One such myokine is interleukin-6 (IL-6), which has been shown to stimulate glucose uptake and increase insulin-stimulated glucose disposal in humans.
IL-6 treatment has been found to increase basal and insulin-stimulated glucose uptake, as well as translocation of GLUT4 to the plasma membrane. This results in enhanced insulin-stimulated glucose disposal in humans in vivo. In addition, IL-6 increases AMP-activated protein kinase (AMPK), which plays a central role in regulating fuel metabolism in skeletal muscle. The activation of AMPK stimulates fatty acid oxidation and may also increase glucose uptake by enhancing insulin signaling transduction.
While the effects of IL-6 on glucose metabolism may be mediated by AMPK, the role of IL-6 in skeletal muscle and adipose tissue in vitro is not entirely clear. Some studies have shown that IL-6 enhances insulin-stimulated glucose transport or glycogen synthesis, while others have found opposite effects. Furthermore, IL-6 selectively stimulates fat metabolism in human skeletal muscle and may have a negative effect on hepatic insulin sensitivity in mice in vivo. However, in healthy humans, acute IL-6 administration does not appear to impair muscle glucose uptake or whole-body glucose disposal.
Overall, IL-6 appears to play a complex role in glucose metabolism, with potential benefits in enhancing insulin-stimulated glucose uptake and disposal. However, further studies are needed to fully understand the effects of IL-6 on glucose metabolism and its interaction with other metabolic pathways.
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Frequently asked questions
Interleukins are a type of cytokine, which are small proteins that act as messengers for the immune system.
Yes, skeletal muscle has been found to produce and secrete interleukin-6 (IL-6), a multifunctional molecule that can act as both a pro-inflammatory and anti-inflammatory cytokine.
Interleukin-6 stimulates hepatic triglyceride secretion and can increase exercise capacity by signalling in osteoblasts. It also enhances insulin secretion by increasing glucagon-like peptide-1 secretion.
Skeletal muscle has also been identified as an endocrine organ that produces and releases cytokines, which have been named "myokines". These include hepatocyte growth factor, insulin-like growth factor (IGF1), fibroblast growth factor, and transforming growth factor β.
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