Muscle–Organ Crosstalk: The Emerging Roles of Myokines

In the paper

“Exercise prior to endotoxin totally blunted the increase in circulating levels of TNF‐α that was observed during a resting situation.”

What the sources say

• Not checked yetcites [113] Starkie, 2003, Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans, FASEB J. source

In the paper

“It was therefore expected that an infusion of rhIL-6 prior to endotoxin administration would also blunt the TNF‐α response in humans and this was in fact what was found (113).”

What the sources say

• Not checked yetcites [113] Starkie, 2003, Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans, FASEB J. source

In the paper

“Our finding in 2000 that skeletal muscle produced and released interleukin-6 (IL-6) into the circulation (5)”

What the sources say

• Not checked yetcites [5] Steensberg, 2000, Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6, J Physiol. source

In the paper

“research during the subsequent years, demonstrating that IL-6 has multiple metabolic effects in other parts of the body (6)”

What the sources say

• Not checked yetcites [6] Pedersen, 2008, Muscle as an endocrine organ: focus on muscle-derived interleukin-6, Physiol Rev. source

In the paper

“Thus, it was obvious that 1 or several humoral factors had to be released from contracting muscles to the blood (3).”

What the sources say

• Not checked yetcites [3] Goldstein, 1961, Humoral nature of hypoglycemia in muscular activity, Am J Physiol. source

In the paper

“It was clear that signaling pathways from exercising skeletal muscle to other organs were not solely mediated via the nervous system, since electrical stimulation of paralyzed muscles in patients with no efferent or afferent nerve impulses induced the same types of physiological changes as were found in healthy human beings (1, 2).”

What the sources say

• Not checked yetcites [1] Kjaer, 1996, Hormonal and metabolic responses to electrically induced cycling during epidural anesthesia in humans, J Appl Physiol (1985). source
• Not checked yetcites [2] Mohr, 1997, Long-term adaptation to electrically induced cycle training in severe spinal cord injured individuals, Spinal Cord. source

In the paper

“During the past couple of decades, it has been apparent that skeletal muscle works as an endocrine organ, which can produce and secrete hundreds of myokines that exert their effects in either autocrine, paracrine, or endocrine manners.”

What the sources say

• Not checked yetcites [5] Steensberg, 2000, Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6, J Physiol. source
• Not checked yetcites [6] Pedersen, 2008, Muscle as an endocrine organ: focus on muscle-derived interleukin-6, Physiol Rev. source

In the paper

“Although the myokine IL-6 is mostly recognized for its regulatory effects in lipid and glucose metabolism, IL-6 also plays important roles in myogenesis.”

What the sources say

• Not checked yetcites [49] Serrano, 2008, Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy, Cell Metab. source

In the paper

“Myokines are also involved in muscle proliferation, differentiation, and regeneration independent of exercise (39, 40).”

What the sources say

• Not checked yetcites [39] Henningsen, 2011, Quantitative analysis of the secretion of the MCP family of chemokines by muscle cells, Mol Biosyst. source
• Not checked yetcites [40] Henningsen, 2010, Dynamics of the skeletal muscle secretome during myoblast differentiation, Mol Cell Proteomics. source

In the paper

“Physical inactivity is associated with high circulating basal levels of IL-6 in humans (55).”

What the sources say

• Not checked yetcites [55] Fischer, 2006, Interleukin-6 in acute exercise and training: what is the biological relevance?, Exerc Immunol Rev.

In the paper

“In addition, myokines with anticancer effects have been recognized (41, 42).”

What the sources say

• Not checked yetcites [41] Hojman, 2018, Molecular mechanisms linking exercise to cancer prevention and treatment, Cell Metab. source
• Not checked yetcites [42] Pedersen, 2016, Voluntary running suppresses tumor growth through epinephrine- and IL-6-dependent NK cell mobilization and redistribution, Cell Metab. source

In the paper

“While IL-6 is characterized as a myokine with endocrine effects, it also works in a paracrine manner exerting metabolic effects within the muscle itself (6, 7).”

What the sources say

• Not checked yetcites [6] Pedersen, 2008, Muscle as an endocrine organ: focus on muscle-derived interleukin-6, Physiol Rev. source
• Not checked yetcites [7] Pedersen, 2012, Muscles, exercise and obesity: skeletal muscle as a secretory organ, Nat Rev Endocrinol. source

In the paper

“Moreover, the acute exercise-induced rise in systemic levels of IL-6 and muscular IL-6 mRNA are diminished by training in humans (56).”

What the sources say

• Not checked yetcites [56] Fischer, 2004, Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle, Am J Physiol Endocrinol Metab. source

In the paper

“A number of other myokines, including IL‑15 (53) and IL-7 (54) have further been demonstrated to possess anabolic features in rodent models.”

What the sources say

• Not checked yetcites [53] Nielsen, 2007, Expression of interleukin-15 in human skeletal muscle effect of exercise and muscle fibre type composition, J Physiol. source
• Not checked yetcites [54] Haugen, 2010, IL-7 is expressed and secreted by human skeletal muscle cells, Am J Physiol Cell Physiol. source

In the paper

“It has further been shown that both IL-6 and LIF activate myotube mTORC1 signaling in a time- and dose-dependent fashion (52).”

What the sources say

• Not checked yetcites [52] Gao, 2017, Acute myotube protein synthesis regulation by IL-6-related cytokines, Am J Physiol Cell Physiol. source

In the paper

“Exercise has been shown to influence the hippocampus more than any other part of the brain.”

In the paper

“In addition, IL-6 increases insulin-stimulated glucose uptake in vitro and in healthy humans in vivo.”

In the paper

“The effects of IL-6 on glucose uptake in vitro was shown to be mediated by activation of adenosine 5′-monophosphate-activated protein kinase (AMPK) (58).”

What the sources say

• Not checked yetcites [58] Carey, 2006, Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase, Diabetes. source

In the paper

“Several other studies have described that IL-6 can increase intramyocellular (58-60) or whole body (61) fatty acid oxidation via AMPK activation (58, 62).”

What the sources say

• Not checked yetcites [58] Carey, 2006, Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase, Diabetes. source
• Not checked yetcites [59] Bruce, 2004, Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-alpha, Am J Physiol Endocrinol Metab. source
• Not checked yetcites [60] Petersen, 2005, Acute IL-6 treatment increases fatty acid turnover in elderly humans in vivo and in tissue culture in vitro: evidence that IL-6 acts independently of lipolytic hormones, Am J Physiol.
• Not checked yetcites [61] van Hall, 2003, Interleukin-6 stimulates lipolysis and fat oxidation in humans, J Clin Endocrinol Metab. source
• Not checked yetcites [62] Kahn, 2005, AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism, Cell Metab. source

In the paper

“Recent evidence shows that musclin abolishes muscle atrophy related with cancer in mice (66).”

What the sources say

• Not checked yetcites [66] Re Cecconi, 2019, Myokine induced by aerobic exercise, retards muscle atrophy during cancer cachexia in mice, Cancers. source

In the paper

“Rodent studies demonstrate increased BDNF mRNA and BDNF protein within the hippocampus in response to wheel running for 1-8 weeks (87-92).”

What the sources say

• Not checked yetcites [87] Neeper, 1995, Exercise and brain neurotrophins, Nature. source
• Not checked yetcites [88] Liu, 2018, Exercise-mediated neurogenesis in the hippocampus via BDNF, Front Neurosci. source
• Not checked yetcites [89] Oliff, 1998, Exercise-induced regulation of brain-derived neurotrophic factor (BDNF) transcripts in the rat hippocampus, Brain Res Mol Brain Res. source
• Not checked yetcites [90] Van Hoomissen, 2003, Effects of chronic exercise and imipramine on mRNA for BDNF after olfactory bulbectomy in rat, Brain Res. source
• Not checked yetcites [91] Farmer, 2004, Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo, Neuroscience. source
• Not checked yetcites [92] Adlard, 2005, The exercise-induced expression of BDNF within the hippocampus varies across life-span, Neurobiol Aging. source

In the paper

“In general, it is found that physical activity decreases the rate of cognitive decline in healthy people and in people with neurodegenerative disorders across the life span (73).”

What the sources say

• Not checked yetcites [73] Voss, 2011, Exercise, brain, and cognition across the life span, J Appl Physiol (1985). source

In the paper

“Evidence is accumulating that physical exercise has positive health effects on cognitive function and brain health (67, 68).”

What the sources say

• Not checked yetcites [67] Cotman, 2007, Exercise builds brain health: key roles of growth factor cascades and inflammation, Trends Neurosci. source
• Not checked yetcites [68] Mattson, 2012, Energy intake and exercise as determinants of brain health and vulnerability to injury and disease, Cell Metab. source

In the paper

“BDNF appears to play a dominant role in mediating the effects of exercise on hippocampus (86).”

What the sources say

• Not checked yetcites [86] Loprinzi, 2019, A brief primer on the mediational role of BDNF in the exercise-memory link, Clin Physiol Funct Imaging. source

In the paper

“Studies in humans show that BDNF is released from the brain during a bout of bicycle exercise (95, 96)”

What the sources say

• Not checked yetcites [95] Rasmussen, 2009, Evidence for a release of brain-derived neurotrophic factor from the brain during exercise, Exp Physiol. source
• Not checked yetcites [96] Seifert, 2010, Endurance training enhances BDNF release from the human brain, Am J Physiol Regul Integr Comp Physiol. source

In the paper

“Furthermore, BDNF has been shown to be mechanistically linked to exercise-induced improvement in cognitive functions, such as memory and learning (93, 94).”

What the sources say

• Not checked yetcites [93] Vaynman, 2004, Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition, Eur J Neurosci. source
• Not checked yetcites [94] Vaynman, 2004, Exercise induces BDNF and synapsin I to specific hippocampal subfields, J Neurosci Res. source

In the paper

“Musclin has been identified as an exercise-induced factor (64) promoting skeletal muscle mitochondrial biogenesis in mice (65).”

What the sources say

• Not checked yetcites [64] Nishizawa, 2004, Musclin, a novel skeletal muscle-derived secretory factor, J Biol Chem. source
• Not checked yetcites [65] Subbotina, 2015, Musclin is an activity-stimulated myokine that enhances physical endurance, Proc Natl Acad Sci U S A. source

In the paper

“In contrast, BDNF is identified as a myokine capable of enhancing AMPK activation and hence lipid oxidation in an autocrine or paracrine manner (63).”

What the sources say

• Not checked yetcites [63] Matthews, 2009, Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase, Diabetologia. source

In the paper

“Recent findings suggest that a muscle–brain endocrine loop exists, which at least in part may be mediated by myokine signaling.”

In the paper

“Thus, when recombinant human IL-6 (rhIL-6) was infused into healthy humans together with a hyperinsulinemic, euglycemic clamp, it improved peripheral insulin-stimulated glucose uptake.”

In the paper

“Circulating levels of FSTL1 may work as a biomarker as high concentrations of FSTL1 are seen in patients with systolic and diastolic heart failure (196, 197), and as FSTL1 levels exhibit prognostic significance in the acute coronary syndrome (198).”

What the sources say

• Not checked yetcites [196] El-Armouche, 2011, Follistatin-like 1 in chronic systolic heart failure: a marker of left ventricular remodeling, Circ Heart Fail. source
• Not checked yetcites [197] Tanaka, 2016, Follistatin like 1 regulates hypertrophy in heart failure with preserved ejection fraction, JACC Basic Transl Sci. source
• Not checked yetcites [198] Ogura, 2012, Therapeutic impact of follistatin-like 1 on myocardial ischemic injury in preclinical models, Circulation. source

In the paper

“Physical inactivity is associated with low-grade chronic inflammation, not least when a physical inactive lifestyle is associated with obesity (29, 142, 144, 145, 207-210).”

What the sources say

• Not checked yetcites [29] Benatti, 2015, Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation, Nat Rev Rheumatol. source
• Not checked yetcites [142] Pedersen, 2017, Anti-inflammatory effects of exercise: role in diabetes and cardiovascular disease, Eur J Clin Invest. source
• Not checked yetcites [144] Karstoft, 2016, Exercise and type 2 diabetes: focus on metabolism and inflammation, Immunol Cell Biol. source
• Not checked yetcites [145] Knudsen, 2015, Targeting inflammation through a physical active lifestyle and pharmaceuticals for the treatment of type 2 diabetes, Curr Diab Rep. source
• Not checked yetcites [207] Petersen, 2006, The role of IL-6 in mediating the anti-inflammatory effects of exercise, J Physiol Pharmacol.
• Not checked yetcites [208] Petersen, 2005, The anti-inflammatory effect of exercise, J Appl Physiol (1985). source
• Not checked yetcites [209] Pedersen, 2003, Muscle-derived interleukin-6: lipolytic, anti-inflammatory and immune regulatory effects, Pflugers Arch. source
• Not checked yetcites [210] Pedersen, 2006, The anti-inflammatory effect of exercise: its role in diabetes and cardiovascular disease control, Essays Biochem. source

In the paper

“During exercise, muscle works as an immunoregulatory organ with impact on leukocyte subset trafficking and inflammation (201) (Fig. 6).”

What the sources say

• Not checked yetcites [201] Duggal, 2019, Can physical activity ameliorate immunosenescence and thereby reduce age-related multi-morbidity?, Nat Rev Immunol. source

In the paper

“There are some indications that the exercise-induced rise in cortisol is mediated by IL-6.”

What the sources say

• Not checked yetcites [112] Steensberg, 2003, IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans, Am J Physiol Endocrinol Metab. source

In the paper

“Using a dog model, it was recently shown that FSTL1 can positively regulate myocardial substrate metabolism, in vivo (199).”

What the sources say

• Not checked yetcites [199] Seki, 2018, Acute and chronic increases of circulating FSTL1 normalize energy substrate metabolism in pacing-induced heart failure, Circ Heart Fail. source

In the paper

“During exercise, lymphocytes and neutrophils are mobilized to the blood.”

What the sources say

• Not checked yetcites [202] McCarthy, 1988, The leucocytosis of exercise. A review and model, Sports Med. source
• Not checked yetcites [203] Pedersen, 2000, Exercise and the immune system: regulation, integration, and adaptation, Physiol Rev. source

In the paper

“Elimination of muscle AMPK led to a weakening of skin structure, whereas IL-15 injections mimic some of the anti-aging effects of exercise on murine skin.”

What the sources say

• Not checked yetcites [200] Crane, 2015, Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging, Aging Cell. source

In the paper

“Tarnopolsky and colleagues (200) demonstrated that endurance exercise improves age-associated skin changes in both mice and humans.”

What the sources say

• Not checked yetcites [200] Crane, 2015, Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging, Aging Cell. source

In the paper

“Follistatin-like 1 (FSTL1) was shown to be produced by both skeletal and cardiac muscle cells and is also termed a cardiokine (193).”

What the sources say

• Not checked yetcites [193] Shimano, 2012, Cardiokines: recent progress in elucidating the cardiac secretome, Circulation. source

In the paper

“IL-15 injections mimic some of the anti-aging effects of exercise on murine skin.”

What the sources say

• Not checked yetcites [200] Crane, 2015, Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging, Aging Cell. source

In the paper

“high concentrations of FSTL1 are seen in patients with systolic and diastolic heart failure (196, 197)”

What the sources say

• Not checked yetcites [196] El-Armouche, 2011, Follistatin-like 1 in chronic systolic heart failure: a marker of left ventricular remodeling, Circ Heart Fail. source
• Not checked yetcites [197] Tanaka, 2016, Follistatin like 1 regulates hypertrophy in heart failure with preserved ejection fraction, JACC Basic Transl Sci. source

In the paper

“The study supports the idea that exercise retards skin aging via a mechanism that involves muscle-derived IL-15.”

What the sources say

• Not checked yetcites [200] Crane, 2015, Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging, Aging Cell. source

In the paper

“FSTL1 levels exhibit prognostic significance in the acute coronary syndrome (198).”

What the sources say

• Not checked yetcites [198] Ogura, 2012, Therapeutic impact of follistatin-like 1 on myocardial ischemic injury in preclinical models, Circulation. source

In the paper

“They showed that exercise regulates muscular IL-15 expression via skeletal muscle AMPK.”

What the sources say

• Not checked yetcites [200] Crane, 2015, Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging, Aging Cell. source

In the paper

“A recent murine study suggested that IL-6 may induce either pro- or anti-inflammatory actions depending on cell source (215).”

What the sources say

• Not checked yetcites [215] Han, 2020, Regulation of adipose tissue inflammation by interleukin 6, Proc Natl Acad Sci U S A. source

In the paper

“IL‐10 inhibits synthesis of TNF‐α (212).”

What the sources say

• Not checked yetcites [212] Opp, 1995, Interleukin-10 (cytokine synthesis inhibitory factor) acts in the central nervous system of rats to reduce sleep, J Neuroimmunol. source

In the paper

“Thus, IL-6 promotes an increase in the production of the anti-inflammatory cytokines, IL‐1 receptor antagonist (IL‐1ra) and IL‐10 (112).”

What the sources say

• Not checked yetcites [112] Steensberg, 2003, IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans, Am J Physiol Endocrinol Metab. source

In the paper

“Together these data show that an acute bout of exercise induces anti‐inflammatory effects that may at least partially be mediated by IL‐6, not excluding other anti-inflammatory factors such as adrenaline and cortisol, as previously discussed (142).”

What the sources say

• Not checked yetcites [142] Pedersen, 2017, Anti-inflammatory effects of exercise: role in diabetes and cardiovascular disease, Eur J Clin Invest. source

In the paper

“The exercise-induced acute increase in IL‐6 stimulates an anti-inflammatory systemic environment.”

In the paper

“A few mechanistic studies have demonstrated a potential role of other myokines, including Oncostatin M, irisin, and SPARC in the suppression of breast and colon cancer growth (41, 224-227).”

What the sources say

• Not checked yetcites [41] Hojman, 2018, Molecular mechanisms linking exercise to cancer prevention and treatment, Cell Metab. source
• Not checked yetcites [224] Hojman, 2011, Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth, Am J Physiol Endocrinol Metab. source
• Not checked yetcites [225] Aoi, 2013, A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise, Gut. source
• Not checked yetcites [226] Lucia, 2016, Muscling in on cancer, N Engl J Med. source
• Not checked yetcites [227] Manole, 2018, Myokines as possible therapeutic targets in cancer cachexia, J Immunol Res. source

In the paper

“Long-term anti-inflammatory effects are facilitated via exercise-training reduction in abdominal fat (216).”

What the sources say

• Not checked yetcites [216] Rosenkilde, 2016, Maintenance of improvements in fitness and fatness 1 year after a 3-month lifestyle intervention in overweight men, Eur J Clin Nutr. source

In the paper

“The effects of exercise on cancer growth were mediated via a direct regulation of natural killer cells by a mechanism that involved epinephrine-dependent mobilization of natural killer cells to the circulation and an IL-6-dependent redistribution to tumors.”

What the sources say

• Not checked yetcites [42] Pedersen, 2016, Voluntary running suppresses tumor growth through epinephrine- and IL-6-dependent NK cell mobilization and redistribution, Cell Metab. source
• Not checked yetcites [222] Moore, 2016, Association of leisure-time physical activity with risk of 26 types of cancer in 1.44 million adults, JAMA Intern Med. source

In the paper

“Blocking IL-6 signaling during exercise abolished the exercise-induced inhibition of tumor growth.”

What the sources say

• Not checked yetcites [42] Pedersen, 2016, Voluntary running suppresses tumor growth through epinephrine- and IL-6-dependent NK cell mobilization and redistribution, Cell Metab. source
• Not checked yetcites [222] Moore, 2016, Association of leisure-time physical activity with risk of 26 types of cancer in 1.44 million adults, JAMA Intern Med. source

In the paper

“In fact, an association has been established between physical inactivity and visceral fat in both rodents (217) and humans (133, 218-220).”

What the sources say

• Not checked yetcites [217] Laye, 2007, Inactivity induces increases in abdominal fat, J Appl Physiol (1985). source
• Not checked yetcites [133] Olsen, 2008, Metabolic responses to reduced daily steps in healthy nonexercising men, JAMA. source
• Not checked yetcites [218] Krogh-Madsen, 2014, Normal physical activity obliterates the deleterious effects of a high-caloric intake, J Appl Physiol (1985). source
• Not checked yetcites [219] Krogh-Madsen, 2010, A 2-wk reduction of ambulatory activity attenuates peripheral insulin sensitivity, J Appl Physiol (1985). source
• Not checked yetcites [220] Harder-Lauridsen, 2017, The effect of alternate-day caloric restriction on the metabolic consequences of 8 days of bed rest in healthy lean men: a randomized trial, J Appl Physiol (1985). source

In the paper

“IL‐1ra inhibits IL‐1β signal transduction (211) and IL‐10 inhibits synthesis of TNF‐α (212).”

What the sources say

• Not checked yetcites [211] Dinarello, 1994, The interleukin-1 family: 10 years of discovery, Faseb J. source

In the paper

“Therefore, the anti-inflammatory effects of physical training may mediate some of the protective effects of exercise on cancer development (41).”

What the sources say

• Not checked yetcites [41] Hojman, 2018, Molecular mechanisms linking exercise to cancer prevention and treatment, Cell Metab. source

In the paper

“Epidemiological studies suggest that physical activity in leisure time reduces the risk of at least 13 different cancer types (41, 42, 222, 223).”

What the sources say

• Not checked yetcites [41] Hojman, 2018, Molecular mechanisms linking exercise to cancer prevention and treatment, Cell Metab. source
• Not checked yetcites [42] Pedersen, 2016, Voluntary running suppresses tumor growth through epinephrine- and IL-6-dependent NK cell mobilization and redistribution, Cell Metab. source
• Not checked yetcites [222] Moore, 2016, Association of leisure-time physical activity with risk of 26 types of cancer in 1.44 million adults, JAMA Intern Med. source
• Not checked yetcites [223] Christensen, 2018, Exercise training in cancer control and treatment, Compr Physiol. source

In the paper

“Moreover, it was shown that IL‐6‐deficient knockout mice have elevated levels of TNF‐α (214).”

What the sources say

• Not checked yetcites [214] Mizuhara, 1994, T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6, J Exp Med. source

In the paper

“People who are physically active after a diagnosis of prostate cancer, colorectal cancer, and breast cancer have a higher survival rate than physically inactive people suffering from the same cancer types (121).”

What the sources say

• Not checked yetcites [121] Pedersen, 2019, The physiology of optimizing health with a focus on exercise as medicine, Annu Rev Physiol. source

In the paper

“Thereby, a vicious circle of chronic inflammation is established (29).”

What the sources say

• Not checked yetcites [29] Benatti, 2015, Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation, Nat Rev Rheumatol. source

In the paper

“Previous studies in cultured human monocytes have shown that IL‐6 prevents endotoxin-induced TNF‐α production (213).”

What the sources say

• Not checked yetcites [213] Schindler, 1990, Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF, Blood. source

In the paper

“Running mice demonstrated a marked reduction in tumor volume and incidence across 6 different tumor models.”

What the sources say

• Not checked yetcites [42] Pedersen, 2016, Voluntary running suppresses tumor growth through epinephrine- and IL-6-dependent NK cell mobilization and redistribution, Cell Metab. source
• Not checked yetcites [222] Moore, 2016, Association of leisure-time physical activity with risk of 26 types of cancer in 1.44 million adults, JAMA Intern Med. source

In the paper

“The findings in mice indicate that IL-6 may have a role in mediating anti-cancer effects.”

In the paper

“The finding of opposite actions of IL-6, depending of the cell source, appeared to be due to a switch of IL6 signaling from a canonical mode (myeloid cells) to a noncanonical trans-signaling mode (adipocytes and muscle) which involved increased expression of the ADAM10/17 metalloprotease that enhances trans-signaling via the soluble IL6 receptor α (215).”

What the sources say

• Not checked yetcites [215] Han, 2020, Regulation of adipose tissue inflammation by interleukin 6, Proc Natl Acad Sci U S A. source

In the paper

“We infused a very low dose of Escherichia coli endotoxin to healthy subjects, who were randomized to either rest or exercise prior to the endotoxin administration (113).”

What the sources say

• Not checked yetcites [113] Starkie, 2003, Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans, FASEB J. source

In the paper

“However, the biological identification of several myokines has turned these molecules into useful biomarkers for monitoring the amount, intensity, and mode of exercise that is sufficient to induce specific physiological and metabolic responses for people with, for example, cancer, diabetes, or neurodegenerative diseases.”

In the paper

“it is likely that the detrimental effects of lack of exercise to some degree is mediated by a lack of myokine release and/or resistance to the effects of myokines.”