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Cited by 514Exercise and Physiological ResponsesAdipokines, Inflammation, and Metabolic DiseasesPhysical Activity and Health

Exercise as a Mean to Control Low‐Grade Systemic Inflammation

Open access
Mathur, Neha, Pedersen, Bente Klarlund·2008·Mediators of Inflammation
DOI 10.1155/2008/109502PMC PMC2615833
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Abstract

Chronic noncommunicable diseases (CNCDs), which include cardiovascular disease, some cancers, for example, colon cancer, breast cancer, and type 2 diabetes, are reaching epidemic proportions worldwide. It has now become clear that low‐grade chronic inflammation is a key player in the pathogenesis of most CNCDs. Given that regular exercise offers protection against all causes of mortality, primarily by protection against atherosclerosis and insulin resistance, we suggest that exercise may exert some of its beneficial health effects by inducing anti‐inflammatory actions. Recently, IL‐6 was introduced as the first myokine, defined as a cytokine, which is produced and released by contracting skeletal muscle fibres, exerting its effects in other organs of the body. We suggest that skeletal muscle is an endocrine organ and that myokines may be involved in mediating the beneficial effects against CNCDs associated with low‐grade inflammation.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review argues that regular exercise protects against chronic noncommunicable diseases (CNCDs) partly through anti-inflammatory actions, with contracting skeletal muscle acting as an endocrine organ that releases myokines—chiefly IL-6. It proposes that the acute IL-6 response to exercise suppresses TNF-α and may thereby counter the low-grade systemic inflammation underlying atherosclerosis and insulin resistance.

Key findings

  • Low-grade chronic inflammation is characterized by a 2- to 3-fold elevation in systemic concentrations of pro- and anti-inflammatory cytokines, cytokine antagonists, and C-reactive protein (CRP); CRP is described as a stronger independent risk factor for cardiovascular disease than LDL cholesterol.
  • Exercise provokes a cytokine response distinct from sepsis: the classical proinflammatory cytokines TNF-α and IL-1β generally do not increase, whereas circulating IL-6 rises exponentially (up to 100-fold) and declines postexercise; the magnitude depends on exercise duration, intensity, and muscle mass involved.
  • In an experimental human endotoxin model, resting subjects showed a 2- to 3-fold increase in circulating TNF-α, whereas 3 hours of ergometer cycling (endotoxin given at 2.5 hours) "totally blunted" the TNF-α response; the effect could be mimicked by IL-6 infusion.
  • TNF-α is presented as a direct pathogenic player in insulin resistance: infusion into healthy humans impaired skeletal muscle glucose uptake via altered insulin signalling (increased p70 S6 kinase, ERK-1/2, JNK; increased serine and reduced tyrosine phosphorylation of IRS-1; impaired Akt substrate 160 phosphorylation), and increased whole-body lipolysis by 40%. In contrast, in vivo human studies provide "little or no evidence" that IL-6 is a direct player in the metabolic syndrome; IL-6 is instead identified as a novel lipolytic factor.

Methods

  • Narrative review; no primary data collection or systematic search strategy is described.
  • Synthesizes cross-sectional studies (physical inactivity associated with low-grade systemic inflammation in healthy subjects, elderly people, and patients with intermittent claudication), longitudinal training studies (reductions in CRP), and mechanistic human infusion/cell-culture studies.
  • Describes one experimental human model in detail: healthy volunteers randomized to rest or exercise prior to a low-dose *E. coli* endotoxin injection, with TNF-α response as the outcome.

Limitations

  • Stated by the paper: the link between the acute anti-inflammatory effects of exercise and its long-term benefits "has not yet been proven"; an alternative explanation offered is that exercise protects against atherosclerosis and only indirectly against vascular and systemic inflammation.
  • Stated by the paper: the role of IL-6 in insulin resistance is "highly controversial," with human circulating IL-6 levels shown to be associated or not associated with insulin resistance across studies.
  • Evident from the text: as a narrative review it relies on cited literature rather than a systematic, reproducible search, and several key mechanistic claims rest on animal or cell-culture work (e.g., IL-6 knockout mice, 3T3-L1 adipocytes) whose supraphysiological doses the authors themselves note are "probably not relevant to human physiology."

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1155/2008/109502

Cites

83 of 83 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 105 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    TNF-α directly impairs glucose uptake and metabolism by altering insulin signal transduction.

    “TNF-α directly impaired glucose uptake and metabolism by altering insulin signal transduction.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [44] Plomgaard P Bouzakri K Krogh-Madsen R Mittendorfer B Zierath JR Pedersen BK Tumor necrosis factor-α induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation Diabetes 2005 54 10 2939 2945 16186396 source

      Not checked in the free run.

  • Findingcitation

    These signalling effects are associated with impaired phosphorylation of Akt substrate 160, the most proximal step in the canonical insulin signalling cascade regulating GLUT4 translocation and glucose uptake.

    “These signalling effects were associated with impaired phosphorylation of Akt substrate 160, the most proximal step identified in the canonical insulin signalling cascade regulating GLUT4 translocation and glucose uptake.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [44] Plomgaard P Bouzakri K Krogh-Madsen R Mittendorfer B Zierath JR Pedersen BK Tumor necrosis factor-α induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation Diabetes 2005 54 10 2939 2945 16186396 source

      Not checked in the free run.

  • Findingown data

    In resting subjects, endotoxin induced a 2- to 3-fold increase in circulating levels of TNF-α.

    “In resting subjects, endotoxin induced a 2- to 3-fold increase in circulating levels of TNF-α.”
    Quote in the paperSubstantial claim
  • Findingown data

    When subjects performed 3 hours of ergometer cycling and received the endotoxin bolus at 2.5 hours, the TNF-α response was totally blunted.

    “In contrast, when the subjects performed 3 hours of ergometer cycling and received the endotoxin bolus at 2.5 hours, the TNF-α response was totally blunted.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Low-grade chronic inflammation is a key player in the pathogenesis of most chronic noncommunicable diseases.

    “It has now become clear that low-grade chronic inflammation is a key player in the pathogenesis of most CNCDs.”
    • Also stated in: § 1. INTRODUCTION · boosted
      “It has now become clear that low-grade chronic inflammation is a key player in the pathogenesis of most NCDCs.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [5] Libby P Inflammation in atherosclerosis Nature 2002 420 6917 868 874 12490960 source

      Not checked in the free run.

    • cites [6] Packard RRS Libby P Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction Clinical Chemistry 2008 54 1 24 38 18160725 source

      Not checked in the free run.

    • cites [7] Dandona P Aljada A Bandyopadhyay A Inflammation: the link between insulin resistance, obesity and diabetes Trends in Immunology 2004 25 1 4 7 14698276 source

      Not checked in the free run.

    • cites [8] Petersen AMW Pedersen BK The anti-inflammatory effect of exercise Journal of Applied Physiology 2005 98 4 1154 1162 15772055 source

      Not checked in the free run.

  • May combine two claims. 26

  • May combine two claims.

    Findingcitation

    TNF-α infusion induces insulin resistance in skeletal muscle of healthy humans without an effect on endogenous glucose production.

    “When TNF-α was infused into healthy humans, we found that TNF-α induces insulin resistance in skeletal muscle, without an effect on endogenous glucose production.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [44] Plomgaard P Bouzakri K Krogh-Madsen R Mittendorfer B Zierath JR Pedersen BK Tumor necrosis factor-α induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation Diabetes 2005 54 10 2939 2945 16186396 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    IL-6 increases the glucose infusion rate and glucose oxidation without affecting suppression of endogenous glucose production during a hyperinsulinemic euglycemic clamp in healthy humans.

    “Recently, we demonstrated that IL-6 increased the glucose infusion rate [56] and glucose oxidation without affecting the suppression of endogenous glucose production during a hyperinsulinemic euglycemic clamp in healthy humans.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Carey AL Steinberg GR Macaulay SL Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase Diabetes 2006 55 10 2688 2697 17003332 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    TNF-α infusion increases phosphorylation of p70 S6 kinase, ERK-1/2, and JNK, with increased serine and reduced tyrosine phosphorylation of IRS-1.

    “TNF-alpha infusion increased phosphorylation of p70 S6 kinase, extracellular signal-regulated kinase-1/2, and c-Jun NH(2)-terminal kinase, concomitant with increased serine and reduced tyrosine phosphorylation of insulin receptor substrate-1.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [44] Plomgaard P Bouzakri K Krogh-Madsen R Mittendorfer B Zierath JR Pedersen BK Tumor necrosis factor-α induces skeletal muscle insulin resistance in healthy human subjects via inhibition of Akt substrate 160 phosphorylation Diabetes 2005 54 10 2939 2945 16186396 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    IL-6 is produced and released by contracting skeletal muscle fibres and exerts effects in other organs of the body.

    “Recently, IL-6 was introduced as the first myokine, defined as a cytokine, which is produced and released by contracting skeletal muscle fibres, exerting its effects in other organs of the body.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [18] Pedersen BK Steensberg A Fischer C Searching for the exercise factor: is IL-6 a candidate? Journal of Muscle Research and Cell Motility 2003 24 2-3 113 119 14609022 source

      Not checked in the free run.

    • cites [19] Febbraio MA Pedersen BK Contraction-induced myokine production and release: is skeletal muscle an endocrine organ? Exercise and Sport Sciences Reviews 2005 33 3 114 119 16006818 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Regular exercise offers protection against all causes of mortality, primarily by protection against atherosclerosis and insulin resistance.

    “regular exercise offers protection against all causes of mortality, primarily by protection against atherosclerosis and insulin resistance”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [9] Myers J Kaykha A George S Fitness versus physical activity patterns in predicting mortality in men American Journal of Medicine 2004 117 12 912 918 15629729 source

      Not checked in the free run.

    • cites [10] Khaw KT Wareham N Bingham S Welch A Luben R Day N Combined impact of health behaviours and mortality in men and women: the EPIC-Norfolk prospective population study PLoS Medicine 2008 5 1 p. e12 18184033 PMC2174962 source

      Not checked in the free run.

    • cites [11] Sui X LaMonte MJ Laditka JN Cardiorespiratory fitness and adiposity as mortality predictors in older adults Journal of the American Medical Association 2007 298 21 2507 2516 18056904 PMC2692959 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Regular physical activity offers protection against, and may be useful as a treatment for, a wide variety of chronic diseases associated with low-grade inflammation.

    “Regular physical activity offers protection against, and may be useful as a treatment for a wide variety of, chronic diseases associated with low-grade inflammation [12].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Pedersen BK Saltin B Evidence for prescribing exercise as therapy in chronic disease Scandinavian Journal of Medicine & Science in Sports 2006 16 supplement 1 3 63 16451303 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Skeletal muscle, by contraction, stimulates production and release of myokines, which may influence metabolism and modify cytokine production in tissue and organs.

    “The discovery of contracting muscle as a cytokine-producing organ opens a new paradigm; skeletal muscle is an endocrine organ that, by contraction, stimulates the production and release of myokines, which may influence metabolism and modify cytokine production in tissue and organs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Type 2 diabetes, obesity, and cardiovascular disease are related to a state of low-grade systemic inflammation.

    “Type 2 diabetes, obesity, and cardiovascular disease are related to a state of low-grade systemic inflammation [7, 27–29].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [7] Dandona P Aljada A Bandyopadhyay A Inflammation: the link between insulin resistance, obesity and diabetes Trends in Immunology 2004 25 1 4 7 14698276 source

      Not checked in the free run.

    • cites [27] Gleeson M Immune function in sport and exercise Journal of Applied Physiology 2007 103 2 693 699 17303714 source

      Not checked in the free run.

    • cites [28] Pedersen BK Fischer CP Physiological roles of muscle-derived interleukin-6 in response to exercise Current Opinion in Clinical Nutrition and Metabolic Care 2007 10 3 265 271 17414493 source

      Not checked in the free run.

    • cites [29] Alexandraki K Piperi C Kalofoutis C Singh J Alaveras A Kalofoutis A Inflammatory process in type 2 diabetes: the role of cytokines Annals of the New York Academy of Sciences 2006 1084 89 117 17151295 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    TNF-α infusion increases whole-body lipolysis by 40% with a concomitant increase in FFA clearance, but with no changes in skeletal muscle FFA uptake, release, or oxidation.

    “Moreover, it was recently demonstrated that TNF-alpha infusion increases whole-body lipolysis by 40% with a concomitant increase in FFA clearance, but with no changes in skeletal muscle FFA uptake, release, or oxidation [45].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [45] Plomgaard P Fischer CP Ibfelt T Pedersen BK van Hall G Tumor necrosis factor-α modulates human in vivo lipolysis The Journal of Clinical Endocrinology & Metabolism 2008 93 2 543 549 18029463 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    IL-6 enhances lipolysis as well as fat oxidation.

    “A number of studies indicate that IL-6 enhances lipolysis, as well as fat oxidation [50, 58].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [50] Petersen EW Carey AL Sacchetti M Acute IL-6 treatment increases fatty acid turnover in elderly humans in vivo and in tissue culture in vitro American Journal of Physiology 2005 288 1 E155 E162 15383370 source

      Not checked in the free run.

    • cites [58] van Hall G Steensberg A Sacchetti M Interleukin-6 stimulates lipolysis and fat oxidation in humans The Journal of Clinical Endocrinology & Metabolism 2003 88 7 3005 3010 12843134 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The IL-6 dose applied in studies showing insulin resistance was supraphysiological and is therefore probably not relevant to human physiology.

    “However, the IL-6 dose applied in the latter studies was supraphysiological, and is therefore probably not relevant to human physiology.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Elevated TNF-α is not secondary to the pathological conditions associated with insulin resistance, but plays a direct pathogenic role in glucose metabolism.

    “Thus, a number of studies indicate that elevated TNF-α is not secondary to the pathological conditions associated with insulin resistance, but that TNF-α plays a direct pathogenic role in glucose metabolism [29, 40].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [29] Alexandraki K Piperi C Kalofoutis C Singh J Alaveras A Kalofoutis A Inflammatory process in type 2 diabetes: the role of cytokines Annals of the New York Academy of Sciences 2006 1084 89 117 17151295 source

      Not checked in the free run.

    • cites [40] Plomgaard P Nielsen AR Fischer CP Associations between insulin resistance and TNF-α in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes Diabetologia 2007 50 12 2562 2571 17928988 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In vitro studies demonstrate that IL-6 can induce insulin resistance in isolated 3T3-L1 adipocytes and in mice.

    “In vitro studies demonstrate that IL-6 can induce insulin resistance in isolated 3T3-L1 adipocytes [51, 52] and in mice [53].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [51] Rotter V Nagaev I Smith U Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-α, overexpressed in human fat cells from insulin-resistant subjects Journal of Biological Chemistry 2003 278 46 45777 45784 12952969 source

      Not checked in the free run.

    • cites [52] Fasshauer M Klein J Lossner U Paschke R Interleukin (IL)-6 mRNA expression is stimulated by insulin, isoproterenol, tumour necrosis factor alpha, growth hormone, and IL-6 in 3T3-L1 adipocytes Hormone and Metabolic Research 2003 35 3 147 152 12734774 source

      Not checked in the free run.

    • cites [53] Kim H-J Higashimori T Park S-Y Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo Diabetes 2004 53 4 1060 1067 15047622 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    When diabetes patients were given an rhIL-6 infusion, plasma insulin decreased to levels comparable with age and BMI-matched healthy controls, indicating that IL-6 enhanced insulin sensitivity.

    “When diabetes patients were given an rhIL-6 infusion, plasma concentrations of insulin decreased to levels comparable with that in age and BMI (body mass index)-matched healthy controls, indicating that the IL-6 enhanced insulin sensitivity [50].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] Petersen EW Carey AL Sacchetti M Acute IL-6 treatment increases fatty acid turnover in elderly humans in vivo and in tissue culture in vitro American Journal of Physiology 2005 288 1 E155 E162 15383370 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    IL-6 deficient mice develop mature-onset obesity and insulin resistance.

    “Consistent with this idea, Wallenius et al. 2002 demonstrated that IL-6 deficient mice developed mature-onset obesity and insulin resistance.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wallenius et al. 2002

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Exercise provokes an increase primarily in IL-6, followed by an increase in IL-1ra and IL-10.

    “Taken together, exercise provokes an increase primarily in IL-6, followed by an increase in IL-1ra and IL-10.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    IL-6 alone markedly increases both lipolysis and fat oxidation in cell culture experiments.

    “cell culture experiments demonstrating that IL-6 alone markedly increases both lipolysis and fat oxidation”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Levels of TNF-α are markedly elevated in anti-IL-6-treated mice and in IL-6-deficient knockout mice, indicating that circulating IL-6 is involved in the regulation of TNF-α levels.

    “and levels of TNF-α are markedly elevated in anti-IL-6-treated mice and in IL-6-deficient knockout mice [67, 68], indicating that circulating IL-6 is involved in the regulation of TNF-α levels.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [67] Matthys P Mitera T Heremans H Van Damme J Billiau A Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in D-galactosamine-sensitized and unsensitized mice Infection and Immunity 1995 63 4 1158 1164 7890366 PMC173128 source

      Not checked in the free run.

    • cites [68] Mizuhara H O'Neill E Seki N T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6 Journal of Experimental Medicine 1994 179 5 1529 1537 8163936 PMC2191474 source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    IL-6 is typically the first cytokine present in the circulation during exercise, its appearance is by far the most marked, and it precedes the appearance of other cytokines.

    “Typically, IL-6 is the first cytokine present in the circulation during exercise, and the appearance of IL-6 in the circulation is by far the most marked and its appearance precedes that of the other cytokines.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    IL-6 and IL-6-regulated acute phase proteins are anti-inflammatory and immunosuppressive, and may negatively regulate the acute-phase response.

    “Interleukin-6 is most often classified as a proinflammatory cytokine, although data also suggest that IL-6 and IL-6-regulated acute phase proteins are anti-inflammatory and immunosuppressive, and may negatively regulate the acute-phase response [20].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Pedersen BK The anti-inflammatory effect of exercise: its role in diabetes and cardiovascular disease control Essays in Biochemistry 2006 42 105 117 17144883 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Circulating IL-6 increases in an exponential fashion up to 100 fold in response to exercise and declines in the postexercise period.

    “The level of circulating IL-6 increases in an exponential fashion (up to 100 fold) in response to exercise, and declines in the postexercise period [60–62].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [60] Febbraio MA Pedersen BK Muscle-derived interleukin-6: mechanisms for activation and possible biological roles The FASEB Journal 2002 16 11 1335 1347 12205025 source

      Not checked in the free run.

    • cites [61] Pedersen BK Hoffman-Goetz L Exercise and the immune system: regulation, integration, and adaptation Physiological Reviews 2000 80 3 1055 1081 10893431 source

      Not checked in the free run.

    • cites [62] Pedersen BK Steensberg A Schjerling P Exercise and interleukin-6 Current Opinion in Hematology 2001 8 3 137 141 11303145 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both TNF-α and IL-6 induce lipolysis, but only IL-6 appears to induce fat oxidation.

    “Of note, whereas it is known that both TNF-α and IL-6 induce lipolysis [40, 49], only IL-6 appears to induce fat oxidation [19, 59].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [40] Plomgaard P Nielsen AR Fischer CP Associations between insulin resistance and TNF-α in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes Diabetologia 2007 50 12 2562 2571 17928988 source

      Not checked in the free run.

    • cites [49] Lyngsø D Simonsen L Bülow J Interleukin-6 production in human subcutaneous abdominal adipose tissue: the effect of exercise The Journal of Physiology 2002 543 1 373 378 12181307 PMC2290472 source

      Not checked in the free run.

    • cites [19] Febbraio MA Pedersen BK Contraction-induced myokine production and release: is skeletal muscle an endocrine organ? Exercise and Sport Sciences Reviews 2005 33 3 114 119 16006818 source

      Not checked in the free run.

    • cites [59] Bruce CR Dyck DJ Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-α American Journal of Physiology 2004 287 4 E616 E621 15149950 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    IL-6 protein is expressed in contracting muscle fibres and IL-6 is released from skeletal muscle during exercise.

    “In addition, it has been demonstrated that the IL-6 protein is expressed in contracting muscle fibres and that IL-6 is released from skeletal muscle during exercise [28].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Pedersen BK Fischer CP Physiological roles of muscle-derived interleukin-6 in response to exercise Current Opinion in Clinical Nutrition and Metabolic Care 2007 10 3 265 271 17414493 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Longitudinal studies show that regular training induces a reduction in CRP level, suggesting that physical activity as such may suppress systemic low-grade inflammation.

    “Moreover, the finding in longitudinal studies that regular training induces a reduction in CRP level suggests that the physical activity as such may suppress systemic low-grade inflammation [74, 75, 79, 80].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [74] Fallon KE Fallon SK Boston T The acute phase response and exercise: court and field sports British Journal of Sports Medicine 2001 35 3 170 173 11375875 PMC1724337 source

      Not checked in the free run.

    • cites [75] Mattusch F Dufaux B Heine O Mertens I Rost R Reduction of the plasma concentration of C-reactive protein following nine months of endurance training International Journal of Sports Medicine 2000 21 1 21 24 10683094 source

      Not checked in the free run.

    • cites [79] Stewart LK Flynn MG Campbell WW The influence of exercise training on inflammatory cytokines and C-reactive protein Medicine & Science in Sports & Exercise 2007 39 10 1714 1719 17909397 source

      Not checked in the free run.

    • cites [80] Goldhammer E Tanchilevitch A Maor I Beniamini Y Rosenschein U Sagiv M Exercise training modulates cytokines activity in coronary heart disease patients International Journal of Cardiology 2005 100 1 93 99 15820291 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Muscle contraction-induced factors, so-called myokines, may be involved in mediating the health beneficial effects of exercise and play important roles in protection against chronic noncommunicable diseases.

    “Muscle contraction-induced factors, so-called myokines, may be involved in mediating the health beneficial effects of exercise and play important roles in the protection against CNCDs, which include cardiovascular conditions, some cancers, and type 2 diabetes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The effect of exercise on the endotoxin-induced TNF-α response could be mimicked by infusion of IL-6, suggesting that IL-6 may be involved in mediating the anti-inflammatory effects of exercise.

    “Moreover, the effect of exercise could be mimicked by infusion of IL-6, suggesting that IL-6 may be involved in mediating the anti-inflammatory effects of exercise [69].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [69] Starkie R Ostrowski SR Jauffred S Febbraio M Pedersen BK Exercise and IL-6 infusion inhibit endotoxin-induced TNF-α production in humans The FASEB Journal 2003 17 8 884 886 12626436 source

      Not checked in the free run.

26 of 26

  • The authors state this as an assumption.

    The origin of TNF in chronic low-grade systemic inflammation is mainly adipose tissue.

    “In the latter case, the stimuli for the cytokine production are not known, but it is assumed that the origin of TNF in chronic low-grade systemic inflammation is mainly the adipose tissue [23–26].”
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Authors
Mathur, N., & Pedersen, B. K.
Affiliations
University of Copenhagen (DK)
Corresponding author
Pedersen, Bente Klarlund
ORCID
Pedersen, Bente Klarlund
Venue
Mediators of Inflammation
Publisher
Wiley
Published
2008-01
Volume
2008
Issue
1
Pages
109502-109502
ISSN
  • 0962-9351 (ISSN-L)
  • 1466-1861
DOI
10.1155/2008/109502
PMC
PMC2615833
OpenAlex
W1987782779
Semantic Scholar
bb0e9ef8fc3f1a7a34688b0fd8f07482ebfc580c
Cited by
514
References
83
Citations by year
2026: 19 · 2025: 22 · 2024: 21 · 2023: 20 · 2022: 36 · 2021: 30 · 2020: 41 · 2019: 28 · 2018: 24 · 2017: 35 · 2016: 33 · 2015: 32 · 2014: 33 · 2013: 24 · 2012: 38
FWCI
3.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Mediators of Inflammation (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Danmarks Grundforskningsfond (02-512-55, LSHM-CT-2004-005272 EXGENESIS)
  • Danish Medical Research Council (02-512-55, LSHM-CT-2004-005272 EXGENESIS)
  • European Commission (02-512-55, LSHM-CT-2004-005272 EXGENESIS)
  • Københavns Universitet (02-512-55, LSHM-CT-2004-005272 EXGENESIS)
Topics
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Physical Activity and Health
Keywords
physical activity, low-grade inflammation, non-communicable diseases, myokines, interleukin-6, anti-inflammatory effects of exercise, insulin resistance, atherosclerosis, type 2 diabetes, cancer
MeSH terms
Humans, Inflammation, Exercise, Interleukin-6, Muscle, Skeletal

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