The anti-inflammatory effects of exercise in the syndromic thread of diabetes and autoimmunity

European Review for Medical and Pharmacological Sciences

Volumn 19, Issue 19, 2015, Pages 3709-3722

  Codella, R ^a,b,c   Luzi, L ^a,b,c   Inverardi, L ^b   Ricordi, C ^b  

^a UNIVERSITY OF MILAN   (Italy)

^b UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^c IRCCS POLICLINICO SAN DONATO   (Italy)

Author keywords

Adipokines; Autoimmunity; Cytokines; Diabetes; Exercise; Immunometabolism; Inflammation; Myokines

Indexed keywords

C REACTIVE PROTEIN; FIBROBLAST GROWTH FACTOR 2; HEAT SHOCK PROTEIN; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; INTERLEUKIN 10; INTERLEUKIN 6; TOLL LIKE RECEPTOR; GLUCOSE BLOOD LEVEL;

ADIPOSE TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; AUTOIMMUNITY; DIABETES MELLITUS; EXERCISE; HUMAN; INFLAMMATION; INSULIN DEPENDENT DIABETES MELLITUS; METABOLIC STRESS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REGULATORY T LYMPHOCYTE; SKELETAL MUSCLE; AUTOIMMUNE DISEASES; DIABETES MELLITUS, TYPE 2; FEMALE; GLUCOSE BLOOD LEVEL; MALE; METABOLISM; MIDDLE AGED; PATHOPHYSIOLOGY; PHYSIOLOGY;

AUTOIMMUNE DISEASES; AUTOIMMUNITY; BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 2; EXERCISE; FEMALE; HUMANS; MALE; MIDDLE AGED;

EID: 84966297264     PISSN: 11283602     EISSN: 22840729     Source Type: Journal    
DOI: None     Document Type: Article

References (136)

1. DAS P, HORTON R. Rethinking our approach to physical activity. Lancet 2012; 380:189-190.
2. LEE IM, SHIROMA EJ, LOBELO F, PUSKA P, BLAIR SN, KATZMARZYK PT, Lancet Physical Activity Series Working Group. Effect of physical inactivity on major non-communicable diseases worldwide: An analysis of burden of disease and life expectancy. Lancet 2012; 380: 219-229.
3. BLAIR SN, CHENG Y, HOLDER JS. Is physical activity or physical fitness more important in defining health benefits? Med Sci Sports Exerc 2001; 33: S379-399; S419-420.
4. JOLLIFFE JA, REES K, TAYLOR RS, THOMPSON D, OLDRIDGE N, EBRAHIM S. Exercise-Based rehabilitation for coronary heart disease. Cochrane Database Syst Rev 2000; 4: CD001800.
5. PIEPOLI MF, CONRAADS V, CORRÀ U, DICKSTEIN K, FRANCIS DP, JAARSMA T, MCMURRAY J, PIESKE B, PIOTROWICZ E, SCHMID JP, ANKER SD, SOLAL AC, FILIPPATOS GS, HOES AW, GIELEN S, GIANNUZZI P, PONIKOWSKI PP. Exercise training in heart failure: From theory to practice. A consensus document of the heart failure association and the european association for cardiovascular prevention and rehabilitation. Eur J Heart Fail 2011; 13: 347-357.
6. LUMB AN, GALLEN IW. Diabetes management for intense exercise. Curr Opin Endocrinol Diabetes Obes 2009; 16: 150-155.
7. GALASSETTI P, RIDDELL MC. Exercise and type 1 diabetes (T1DM). Compr Physiol 2013; 3: 1309-1336.
8. COSTA ROSA LF. Exercise as a time-conditioning effector in chronic disease: A complementary treatment strategy. Evid Based Complement Alternat Med 2004; 1: 63-70.
9. WENTWORTH JM, FOURLANOS S, HARRISON LC. Reappraising the stereotypes of diabetes in the modern diabetogenic environment. Nat Rev Endocrinol 2009; 5: 483-489.
10. FLOREZ JC. Clinical review: The genetics of type 2 diabetes: A realistic appraisal in 2008. J Clin Endocrinol Metab 2008; 93: 4633-4642.
11. FOURLANOS S, DOTTA F, GREENBAUM CJ, PALMER JP, ROLANDSSON O, COLMAN PG, HARRISON LC. Latent autoimmune diabetes in adults (LADA) should be less latent. Diabetologia 2005; 48: 2206-2212.
12. FOURLANOS S, VARNEY MD, TAIT BD, MORAHAN G, HONEYMAN MC, COLMAN PG, HARRISON LC. The rising incidence of type 1 diabetes is accounted for by cases with lower-risk human leukocyte antigen genotypes. Diabetes Care 2008; 31: 1546-1549.
13. LUZI L, CODELLA R, LAURIOLA V, MESSINGER S, ALEJANDRO R, RICORDI C. Immunomodulatory effects of exercise in type 1 diabetes mellitus. Diabetes 2011; 60: A209-A210.
14. KRAUSE MDA S, DE BITTENCOURT PI. Type 1 diabetes: Can exercise impair the autoimmune event? The l-arginine/glutamine coupling hypothesis. Cell Biochem Funct 2008; 26: 406-433.
15. DONATH MY, STØRLING J, MAEDLER K, MANDRUPPOULSEN T. Inflammatory mediators and islet betacell failure: A link between type 1 and type 2 diabetes. J Mol Med (Berl) 2003; 8: 455-470.
16. MUOIO DM, NEWGARD CB. Mechanisms of disease: Molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes. Nat Rev Mol Cell Biol 2008; 9: 193-205.
17. LUDVIGSSON J. Why diabetes incidence increases-a unifying theory. Ann N Y Acad Sci 2006; 1079: 374-382.
18. EHSES JA, PERREN A, EPPLER E, RIBAUX P, POSPISILIK JA, MAOR-CAHN R, GUERIPEL X, ELLINGSGAARD H, SCHNEIDER MK, BIOLLAZ G, FONTANA A, REINECKE M, HOMODELARCHE F, DONATH MY. Increased number of isletassociated macrophages in type 2 diabetes. Diabetes 2007; 56: 2356-2370.
19. BUTCHER MJ, HALLINGER D, GARCIA E, MACHIDA Y, CHAKRABARTI S, NADLER J, GALKINA EV, IMAI Y. Association of proinflammatory cytokines and islet resident leucocytes with islet dysfunction in type 2 diabetes. Diabetologia 2014; 57: 491-501.
20. BROOKS-WORRELL B, NARLA R, PALMER JP. Islet autoimmunity in phenotypic type 2 diabetes patients. Diabetes Obes Metab 2013; 15: 137-140.
21. SARIKONDA G, PETTUS J, PHATAK S, SACHITHANANTHAM S, MILLER JF, WESLEY JD, CADAG E, CHAE J, GANESAN L, MALLIOS R, EDELMAN S, PETERS B, VON HERRATH M. CD8 t-cell reactivity to islet antigens is unique to type 1 while CD4 t-cell reactivity exists in both type 1 and type 2 diabetes. J Autoimmun 2014; 50: 77-82.
22. SUBAUSTE A, GIANANI R, CHANG AM, PLUNKETT C, PIETROPAOLO SL, ZHANG YJ, BARINAS-MITCHELL E, KULLER LH, GALECKI A, HALTER JB, PIETROPAOLO M. Islet autoimmunity identifies a unique pattern of impaired pancreatic beta-cell function, markedly reduced pancreatic beta cell mass and insulin resistance in clinically diagnosed type 2 diabetes. Plos One 2014; 9: e106537.
23. PIETROPAOLO M, BARINAS-MITCHELL E, PIETROPAOLO SL, KULLER LH, TRUCCO M. Evidence of islet cell autoimmunity in elderly patients with type 2 diabetes. Diabetes 2000; 49: 32-38.
24. HOTAMISLIGIL GS. Inflammation and metabolic disorders. Nature 2006; 444: 860-867.
25. SHOELSON SE, LEE J, GOLDFINE AB. Inflammation and insulin resistance. J Clin Invest 2006; 116: 1793-1801.
26. WELLEN KE, HOTAMISLIGIL GS. Inflammation, stress, and diabetes. J Clin Invest 2005; 115: 1111-1119.
27. DANDONA P, ALJADA A, BANDYOPADHYAY A. Inflammation: The link between insulin resistance, obesity and diabetes. Trends Immunol 2004; 25: 4-7.
28. BRUUN JM, LIHN AS, PEDERSEN SB, RICHELSEN B. Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (AT): Implication of macrophages resident in the AT. J Clin Endocrinol Metab 2005; 90: 2282-2289.
29. CINTI S, MITCHELL G, BARBATELLI G, MURANO I, CERESI E, FALOIA E, WANG S, FORTIER M, GREENBERG AS, OBIN MS. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005; 46: 2347-2355.
30. XU H, BARNES GT, YANG Q, TAN G, YANG D, CHOU CJ, SOLE J, NICHOLS A, ROSS JS, TARTAGLIA LA, CHEN H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003; 112:01821-1830.
31. SAMUEL VT, SHULMAN GI. Mechanisms for insulin resistance: Common threads and missing links. Cell 2012; 148: 852-871.
32. CAI D, YUAN M, FRANTZ DF, MELENDEZ PA, HANSEN L, LEE J, SHOELSON SE. Local and systemic insulin resistance resulting from hepatic activation of IKKbeta and NF-kappaB. Nat Med 2005; 11: 183-190.
33. OUCHI N, PARKER JL, LUGUS JJ, WALSH K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol 2011; 11: 85-97.
34. HOTAMISLIGIL GS, SHARGILL NS, SPIEGELMAN BM. Adipose expression of tumor necrosis factor-alpha: Direct role in obesity-linked insulin resistance. Science 1993; 259: 87-91.
35. ZHANG Y, PROENCA R, MAFFEI M, BARONE M, LEOPOLD L, FRIEDMAN JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425-32.
36. FRIEDMAN JM. The function of leptin in nutrition, weight, and physiology. Nutr Rev 2002; 60: S1-14; S68-84, 85-87.
37. FANTUZZI G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 2005; 115: 911-919; quiz 920.
38. CHEN A, MUMICK S, ZHANG C, LAMB J, DAI H, WEINGARTH D, MUDGETT J, CHEN H, MACNEIL DJ, REITMAN ML, QIAN S. Diet induction of monocyte chemoattractant protein-1 and its impact on obesity. Obes Res 2005; 13: 1311-1320.
39. VIARDOT A, HEILBRONN LK, SAMOCHA-BONET D, MACKAY F, CAMPBELL LV, SAMARAS K. Obesity is associated with activated and insulin resistant immune cells. Diabetes Metab Res Rev 2012; 28: 447-454.
40. WINER S, CHAN Y, PALTSER G, TRUONG D, TSUI H, BAHRAMI J, DORFMAN R, WANG Y, ZIELENSKI J, MASTRONARDI F, MAEZAWA Y, DRUCKER DJ, ENGLEMAN E, WINER D, DOSCH HM. Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med 2009; 15: 921-929.
41. NISHIMURA S, MANABE I, NAGASAKI M, ETO K, YAMASHITA H, OHSUGI M, OTSU M, HARA K, UEKI K, SUGIURA S, YOSHIMURA K, KADOWAKI T, NAGAI R. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 2009; 15: 914-920.
42. DEFURIA J, BELKINA AC, JAGANNATHAN-BOGDAN M, SNYDER-CAPPIONE J, CARR JD, NERSESOVA YR, MARKHAM D, STRISSEL KJ, WATKINS AA, ZHU M, ALLEN J, BOUCHARD J, TORALDO G, JASUJA R, OBIN MS, MCDONNELL ME, APOVIAN C, DENIS GV, NIKOLAJCZYK BS. B cells promote inflammation in obesity and type 2 diabetes through regulation of t-cell function and an inflammatory cytokine profile. Proc Natl Acad Sci U S A 2013; 110: 5133-5138.
43. WINER DA, WINER S, SHEN L, WADIA PP, YANTHA J, PALTSER G, TSUI H, WU P, DAVIDSON MG, ALONSO MN, LEONG HX, GLASSFORD A, CAIMOL M, KENKEL JA, TEDDER TF, MCLAUGHLIN T, MIKLOS DB, DOSCH HM, ENGLEMAN EG. B cells promote insulin resistance through modulation of T cells and production of pathogenic igg antibodies. Nat Med 2011; 17: 610-617.
44. MATHIS D, SHOELSON SE. Immunometabolism: An emerging frontier. Nat Rev Immunol 2011; 11: 81.
45. TSAI S, CLEMENTE-CASARES X, REVELO XS, WINER S, WINER DA. Are obesity-related insulin resistance and type 2 diabetes autoimmune diseases? Diabetes 2015; 64: 1886-1897.
46. STANFORD KI, MIDDELBEEK RJ, TOWNSEND KL, LEE MY, TAKAHASHI H, SO K, HITCHCOX KM, MARKAN KR, HELLBACH K, HIRSHMAN MF, TSENG YH, GOODYEAR LJ. A novel role for subcutaneous adipose tissue in exercise-induced improvements in glucose homeostasis. Diabetes 2015; 64: 2002-2014.
47. PEDERSEN BK, FEBBRAIO MA. Muscles, exercise and obesity: Skeletal muscle as a secretory organ. Nat Rev Endocrinol 2012; 8: 457-465.
48. PEDERSEN BK, FEBBRAIO MA. Muscle as an endocrine organ: Focus on muscle-derived interleukin-6. Physiol Rev 2008; 88: 1379-1406.
49. MCPHERRON AC, LAWLER AM, LEE SJ. Regulation of skeletal muscle mass in mice by a new tgf-beta superfamily member. Nature 1997; 387: 83-90.
50. HANSEN J, BRANDT C, NIELSEN AR, HOJMAN P, WHITHAM M, FEBBRAIO MA, PEDERSEN BK, PLOMGAARD P. Exercise induces a marked increase in plasma follistatin: Evidence that follistatin is a contractioninduced hepatokine. Endocrinology 2011; 152: 164-171.
51. ZHAO B, WALL RJ, YANG J. Transgenic expression of myostatin propeptide prevents diet-induced obesity and insulin resistance. Biochem Biophys Res Commun 2005; 337: 248-255.
52. GUO T, JOU W, CHANTURIYA T, PORTAS J, GAVRILOVA O, MCPHERRON AC. Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity. Plos One 2009; 4: e4937.
53. FELDMAN BJ, STREEPER RS, FARESE RV, YAMAMOTO KR. Myostatin modulates adipogenesis to generate adipocytes with favorable metabolic effects. Proc Natl Acad Sci U S A 2006; 103: 15675-15680.
54. ALLEN DL, CLEARY AS, SPEAKER KJ, LINDSAY SF, UYENISHI J, REED JM, MADDEN MC, MEHAN RS. Myostatin, activin receptor IIb, and follistatin-like-3 gene expression are altered in adipose tissue and skeletal muscle of obese mice. Am J Physiol Endocrinol Metab 2008; 294: E918-927.
55. HITTEL DS, BERGGREN JR, SHEARER J, BOYLE K, HOUMARD JA. Increased secretion and expression of myostatin in skeletal muscle from extremely obese women. Diabetes 2009; 58: 30-38.
56. LEE SJ, MCPHERRON AC. Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci U S A 2001; 98: 9306-9311.
57. ALLEN DL, HITTEL DS, MCPHERRON AC. Expression and function of myostatin in obesity, diabetes, and exercise adaptation. Med Sci Sports Exerc 2011; 43: 1828-1835.
58. FEBBRAIO MA, PEDERSEN BK. Muscle-Derived interleukin-6: Mechanisms for activation and possible biological roles. FASEB J 2002; 16: 1335-1347.
59. ELLINGSGAARD H, HAUSELMANN I, SCHULER B, HABIB AM, BAGGIO LL, MEIER DT, EPPLER E, BOUZAKRI K, WUEEST S, MULLER YD, HANSEN AM, REINECKE M, KONRAD D, GASSMANN M, REIMANN F, HALBAN PA, GROMADA J, DRUCKER DJ, GRIBBLE FM, EHSES JA, DONATH MY. Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nat Med 2011; 17: 1481-1489.
60. BOUZAKRI K, PLOMGAARD P, BERNEY T, DONATH MY, PEDERSEN BK, HALBAN PA. Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle. Diabetes 2011; 60: 1111-1121.
61. CAREY AL, STEINBERG GR, MACAULAY SL, THOMAS WG, HOLMES AG, RAMM G, PRELOVSEK O, HOHNEN-BEHRENS C, WATT MJ, JAMES DE, KEMP BE, PEDERSEN BK, FEBBRAIO MA. 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: 2688-2697.
62. KELLY M, KELLER C, AVILUCEA PR, KELLER P, LUO Z, XIANG X, GIRALT M, HIDALGO J, SAHA AK, PEDERSEN BK, RUDERMAN NB. AMPK activity is diminished in tissues of IL-6 knockout mice: The effect of exercise. Biochem Biophys Res Commun 2004; 320: 449-454.
63. MATTHEWS VB, ASTRÖM MB, CHAN MH, BRUCE CR, KRABBE KS, PRELOVSEK O, AKERSTRÖM T, YFANTI C, BROHOLM C, MORTENSEN OH, PENKOWA M, HOJMAN P, ZANKARI A, WATT MJ, BRUUNSGAARD H, PEDERSEN BK, FEBBRAIO MA. 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 2009; 52: 1409-1418.
64. FERRIS LT, WILLIAMS JS, SHEN CL. The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function. Med Sci Sports Exerc 2007; 39: 728-734.
65. CHALDER M, WILES NJ, CAMPBELL J, HOLLINGHURST SP, HAASE AM, TAYLOR AH, FOX KR, COSTELLOE C, SEARLE A, BAXTER H, WINDER R, WRIGHT C, TURNER KM, CALNAN M, LAWLOR DA, PETERS TJ, SHARP DJ, MONTGOMERY AA, LEWIS G. Facilitated physical activity as a treatment for depressed adults: Randomised controlled trial. Br Med J 2012; 344: e2758.
66. STEENSBERG A, FISCHER CP, KELLER C, MØLLER K, PEDERSEN BK. IL-6 enhances plasma il-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab 2003; 285: E433-437.
67. KELLER C, HELLSTEN Y, STEENSBERG A, PEDERSEN BK. Differential regulation of IL-6 and tnf-alpha via calcineurin in human skeletal muscle cells. Cytokine 2006; 36: 141-147.
68. KELLER C, STEENSBERG A, HANSEN AK, FISCHER CP, PLOMGAARD P, PEDERSEN BK. Effect of exercise, training, and glycogen availability on IL-6 receptor expression in human skeletal muscle. J Appl Physiol (1985) 2005; 99: 2075-2079.
69. SERRANO AL, BAEZA-RAJA B, PERDIGUERO E, JARDÍ M, MUÑOZ-CÁNOVES P. Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab 2008; 7: 33-44.
70. AL-SHANTI N, SAINI A, FAULKNER SH, STEWART CE. Beneficial synergistic interactions of tnf-alpha and IL-6 in C2 skeletal myoblasts-potential cross-talk with IGF system. Growth Factors 2008; 26: 61-73.
71. HASHIZUME M, HAYAKAWA N, SUZUKI M, MIHARA M. IL-6/sil-6r trans-signalling, but not tnf-alpha induced angiogenesis in a HUVEC and synovial cell co-culture system. Rheumatol Int 2009; 29: 1449-1454.
72. CAMPBELL IL, HOBBS MV, DOCKTER J, OLDSTONE MB, ALLISON J. Islet inflammation and hyperplasia induced by the pancreatic islet-specific overexpression of interleukin-6 in transgenic mice. Am J Pathol 1994; 145: 157-166.
73. DICOSMO BF, PICARELLA D, FLAVELL RA. Local production of human IL-6 promotes insulitis but retards the onset of insulin-dependent diabetes mellitus in non-obese diabetic mice. Int Immunol 1994; 6: 1829-1837.
74. CHOI SE, CHOI KM, YOON IH, SHIN JY, KIM JS, PARK WY, HAN DJ, KIM SC, AHN C, KIM JY, HWANG ES, CHA CY, SZOT GL, YOON KH, PARK CG. IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo. Transpl Immunol 2004; 13: 43-53.
75. HAMRICK MW. A role for myokines in muscle-bone interactions. Exerc Sport Sci Rev 2011; 39: 43-47.
76. BOSTRÖM P, WU J, JEDRYCHOWSKI MP, KORDE A, YE L, LO JC, RASBACH KA, BOSTRÖM EA, CHOI JH, LONG JZ, KAJIMURA S, ZINGARETTI MC, VIND BF, TU H, CINTI S, HØJLUND K, GYGI SP, SPIEGELMAN BM. A PGC1-a-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012; 481: 463-468.
77. YANG H, CHANG J, CHEN W, ZHAO L, QU B, TANG C, QI Y, ZHANG J. Treadmill exercise promotes interleukin 15 expression in skeletal muscle and interleukin 15 receptor alpha expression in adipose tissue of high-fat diet rats. Endocrine 2013; 43: 579-585.
78. GOLDSTEIN MS. Humoral nature of the hypoglycemic factor of muscular work. Diabetes 1961; 10: 232-234.
79. DELMONTE V, PEIXOTO EM, POGGIOLI R, ENFIELD G, LUZI L, RICORDI C, ALEJANDRO R. Ten years' evaluation of diet, anthropometry, and physical exercise adherence after islet allotransplantation. Transplant Proc 2013; 45: 2025-2028.
80. DELMONTE V, CODELLA R, PIEMONTI L, LA TORRE A, BENEDINI S, MAFFI P, RICORDI C, LUZI L. Effects of exercise in a islet-transplanted half-marathon runner: Outcome on diabetes management, training and metabolic profile. Sport Sciences for Health 2014; 10: 49-52.
81. OSBORN O, OLEFSKY JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med 2012; 18: 363-374.
82. KAWANISHI N, YANO H, YOKOGAWA Y, SUZUKI K. Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet-induced obese mice. Exerc Immunol Rev 2010; 16: 105-118.
83. PETERSEN AM, PEDERSEN BK. The anti-inflammatory effect of exercise. J Appl Physiol (1985) 2005; 98: 1154-1162.
84. MATHUR N, PEDERSEN BK. Exercise as a mean to control low-grade systemic inflammation. Mediators Inflamm 2008; 2008: 109502.
85. ESPOSITO K, PONTILLO A, DI PALO C, GIUGLIANO G, MASELLA M, MARFELLA R, GIUGLIANO D. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: A randomized trial. JAMA 2003; 289: 1799-1804.
86. PEDERSEN BK, AKERSTRÖM TC, NIELSEN AR, FISCHER CP. Role of myokines in exercise and metabolism. J Appl Physiol (1985) 2007; 103: 1093-1098.
87. FISCHER CP. Interleukin-6 in acute exercise and training: What is the biological relevance? Exerc Immunol Rev 2006; 12: 6-33.
88. ESPOSITO K1, NAPPO F, MARFELLA R, GIUGLIANO G, GIUGLIANO F, CIOTOLA M, QUAGLIARO L, CERIELLO A, GIUGLIANO D. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: Role of oxidative stress. Circulation 2002; 106: 2067-2072.
89. STEENSBERG A, VAN HALL G, OSADA T, SACCHETTI M, SALTIN B, KLARLUND PEDERSEN B. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol 2000; 529: 237-242.
90. STEENSBERG A, FEBBRAIO MA, OSADA T, SCHJERLING P, VAN HALL G, SALTIN B, PEDERSEN BK. Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content. J Physiol 2001; 537: 633-639.
91. OSTROWSKI K, HERMANN C, BANGASH A, SCHJERLING P, NIELSEN JN, PEDERSEN BK. A trauma-like elevation of plasma cytokines in humans in response to treadmill running. J Physiol 1998; 513: 889-894.
92. STARKIE R, OSTROWSKI SR, JAUFFRED S, FEBBRAIO M, PEDERSEN BK. Exercise and IL-6 infusion inhibit endotoxin-induced tnf-alpha production in humans. FASEB J 2003; 17: 884-6.
93. OSTROWSKI K, SCHJERLING P, PEDERSEN BK. Physical activity and plasma interleukin-6 in humans-effect of intensity of exercise. Eur J Appl Physiol 2000; 83: 512-515.
94. 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. Infect Immun 1995; 63: 1158-1164.
95. FIERS W. Tumor necrosis factor. Characterization at the molecular, cellular and in vivo level. FEBS Lett 1991; 285: 199-212.
96. FREEMAN BD, BUCHMAN TG. Interleukin-1 receptor antagonist as therapy for inflammatory disorders. Expert Opin Biol Ther 2001; 1: 301-308.
97. DINARELLO CA, SIMON A, VAN DER MEER JWM. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov 2012; 11: 633-652.
98. MOORE KW, DE WAAL MALEFYT R, COFFMAN RL, O'-GARRA A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001; 19: 683-765.
99. MAYNARD CL, WEAVER CT. Diversity in the contribution of interleukin-10 to t-cell-mediated immune regulation. Immunol Rev 2008; 226: 219-233.
100. HONG EG, KO HJ, CHO YR, KIM HJ, MA Z, YU TY, FRIEDLINE RH, KURT-JONES E, FINBERG R, FISCHER MA, GRANGER EL, NORBURY CC, HAUSCHKA SD, PHILBRICK WM, LEE CG, ELIAS JA, KIM JK. Interleukin-10 prevents diet-induced insulin resistance by attenuating macrophage and cytokine response in skeletal muscle. Diabetes 2009; 58: 2525-2535.
101. 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. Int J Sports Med 2000; 21: 21-24.
102. FALLON KE, FALLON SK, BOSTON T. The acute phase response and exercise: Court and field sports. Br J Sports Med 2001; 35: 170-173.
103. PEDERSEN BK, HOFFMAN-GOETZ L. Exercise and the immune system: Regulation, integration, and adaptation. Physiol Rev 2000; 80: 1055-1081.
104. STEWART LK, FLYNN MG, CAMPBELL WW, CRAIG BA, ROBINSON JP, MCFARLIN BK, ET AL. Influence of exercise training and age on CD14+ cell-surface expression of toll-like receptor 2 and 4. Brain Behav Immun 2005; 19: 389-397.
105. KAISHO T, AKIRA S. Toll-Like receptor function and signaling. J Allergy Clin Immunol 2006; 117: 979-987; quiz 988.
106. TAKEDA K, KAISHO T, AKIRA S. Toll-Like receptors. Annu Rev Immunol 2003; 21: 335-376.
107. ATALAY M, OKSALA NK, LAAKSONEN DE, KHANNA S, NAKAO C, LAPPALAINEN J, ROY S, HÄNNINEN O, SEN CK. Exercise training modulates heat shock protein response in diabetic rats. J Appl Physiol (1985) 2004; 97: 605-611.
108. MORIMOTO RI, SANTORO MG. Stress-Inducible responses and heat shock proteins: New pharmacologic targets for cytoprotection. Nat Biotechnol 1998; 16: 833-838.
109. MOYNAGH PN. The nf-kappab pathway. J Cell Sci 2005; 118: 4589-4592.
110. DRÖGE W. Free radicals in the physiological control of cell function. Physiol Rev 2002; 82: 47-95.
111. WENDLING U, FARINE JC. ORAL ADMINISTRATION OF HSPCONTAINING E. Coli extract OM-89 has suppressive effects in autoimmunity. Regulation of autoimmune processes by modulating peripheral immunity towards hsp's? Biotherapy 1998; 10: 223-227.
112. WANG J, SONG H, TANG X, YANG Y, VIEIRA VJ, NIU Y, MA Y. Effect of exercise training intensity on murine tregulatory cells and vaccination response. Scand J Med Sci Sports 2012; 22: 643-652.
113. GLEESON M, BISHOP NC, STENSEL DJ, LINDLEY MR, MASTANA SS, NIMMO MA. The anti-inflammatory effects of exercise: Mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol 2011; 11: 607-615.
114. FERNANDEZ MA, PUTTUR FK, WANG YM, HOWDEN W, ALEXANDER SI, JONES CA. T regulatory cells contribute to the attenuated primary CD8+ and CD4+ T cell responses to herpes simplex virus type 2 in neonatal mice. J Immunol 2008; 180: 1556-1564.
115. SAKAGUCHI S. Naturally arising foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 2005; 6: 345-352.
116. CODELLA R, LANZONI G, ZOSO A, CAUMO A, MONTESANO A, TERRUZZI IM, RICORDI C, LUZI L, INVERARDI L. Moderate intensity training impact on the inflammatory status and glycemic profiles in NOD mice. J Diabetes Res 2015, 2015: 737586.
117. BALDUCCI S, ZANUSO S, NICOLUCCI A, FERNANDO F, CAVALLO S, CARDELLI P, FALLUCCA S, ALESSI E, LETIZIA C, JIMENEZ A, FALLUCCA F, PUGLIESE G. Anti-Inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss. Nutr Metab Cardiovasc Dis 2010; 20: 608-617.
118. BALDUCCI S1, ZANUSO S, NICOLUCCI A, DE FEO P, CAVALLO S, CARDELLI P, FALLUCCA S, ALESSI E, FALLUCCA F, PUGLIESE G. Effect of an intensive exercise intervention strategy on modifiable cardiovascular risk factors in subjects with type 2 diabetes mellitus: A randomized controlled trial: The italian diabetes and exercise study (IDES). Arch Intern Med 2010; 170: 1794-1803.
119. BEAVERS KM, BRINKLEY TE, NICKLAS BJ. Effect of exercise training on chronic inflammation. Clin Chim Acta 2010; 411: 785-793.
120. FIUZA-LUCES C, GARATACHEA N, BERGER NA, LUCIA A. Exercise is the real polypill. Physiology (Bethesda) 2013; 28: 330-358.
121. KADOGLOU NP, ILIADIS F, ANGELOPOULOU N, PERREA D, AMPATZIDIS G, LIAPIS CD, ALEVIZOS M. The anti-inflammatory effects of exercise training in patients with type 2 diabetes mellitus. Eur J Cardiovasc Prev Rehabil 2007; 14: 837-843.
122. NICKLAS BJ, HSU FC, BRINKLEY TJ, CHURCH T, GOODPASTER BH, KRITCHEVSKY SB, PAHOR M. Exercise training and plasma c-reactive protein and interleukin-6 in elderly people. J Am Geriatr Soc 2008; 56: 2045-2052.
123. WALTHER C, MÖBIUS-WINKLER S, LINKE A, BRUEGEL M, THIERY J, SCHULER G, HALBRECHT R. Regular exercise training compared with percutaneous intervention leads to a reduction of inflammatory markers and cardiovascular events in patients with coronary artery disease. Eur J Cardiovasc Prev Rehabil 2008; 15: 107-112.
124. NOBLE EE, BILLINGTON CJ, KOTZ CM, WANG CF. The lighter side of BDNF. Am J Physiol Regul Integr Comp Physiol 2011; 300: R1053-1069.
125. GEFFKEN DF, CUSHMAN M, BURKE GL, POLAK JF, SAKKINEN PA, TRACY RP. Association between physical activity and markers of inflammation in a healthy elderly population. Am J Epidemiol 2001; 153: 242-250.
126. FISCHER CP, PLOMGAARD P, HANSEN AK, PILEGAARD H, SALTIN B, PEDERSEN BK. Endurance training reduces the contraction-induced interleukin-6 mrna expression in human skeletal muscle. Am J Physiol Endocrinol Metab 2004; 287: E1189-1194.
127. LANCASTER GI, KHAN Q, DRYSDALE P, WALLACE F, JEUKENDRUP AE, DRAYSON MT, GLEESON M. The physiological regulation of toll-like receptor expression and function in humans. J Physiol 2005; 563: 945-955.
128. GLEESON M, BISHOP N, OLIVEIRA M, MCCAULEY T, TAULER P, MUHAMAD AS. Respiratory infection risk in athletes: Association with antigen-stimulated IL-10 production and salivary iga secretion. Scand J Med Sci Sports 2012; 22: 410-417.
129. HERBST A, KORDONOURI O, SCHWAB KO, SCHMIDT F, HOLL RW, DPV Initiative of the German Working Group for Pediatric Diabetology Germany. Impact of physical activity on cardiovascular risk factors in children with type 1 diabetes: A multicenter study of 23,251 patients. Diabetes Care 2007; 30: 2098-2100.
130. HUBER J, FRÖHLICH-REITERER EE, SUDI K, SUPPAN E, WEINHANDL G, JASSER-NITSCHE H, AIGNER R, BORKENSTEIN MH. The influence of physical activity on ghrelin and IGF-1/IGFBP-3 levels in children and adolescents with type 1 diabetes mellitus. Pediatr Diabetes 2010; 11: 383-385.
131. PHILLIPS MD, FLYNN MG, MCFARLIN BK, STEWART LK, TIMMERMAN KL. Resistance training at eight-repetition maximum reduces the inflammatory milieu in elderly women. Med Sci Sports Exerc 2010; 42: 314-325.
132. CUFF DJ, MENEILLY GS, MARTIN A, IGNASZEWSKI A, TILDESLEY HD, FROHLICH JJ. Effective exercise modality to reduce insulin resistance in women with type 2 diabetes. Diabetes Care 2003; 26: 2977-2982.
133. JANSSEN I, FORTIER A, HUDSON R, ROSS R. Effects of an energy-restrictive diet with or without exercise on abdominal fat, intermuscular fat, and metabolic risk factors in obese women. Diabetes Care 2002; 25: 431-438.
134. RICE B, JANSSEN I, HUDSON R, ROSS R. Effects of aerobic or resistance exercise and/or diet on glucose tolerance and plasma insulin levels in obese men. Diabetes Care 1999; 22: 684-691.
135. RIECHMAN SE, BALASEKARAN G, ROTH SM, FERRELL RE. Association of interleukin-15 protein and interleukin-15 receptor genetic variation with resistance exercise training responses. J Appl Physiol (1985) 2004; 97: 2214-2219.
136. NIELSEN AR1, MOUNIER R, PLOMGAARD P, MORTENSEN OH, PENKOWA M, SPEERSCHNEIDER T, PILEGAARD H, PEDERSEN BK. Expression of interleukin-15 in human skeletal muscle effect of exercise and muscle fibre type composition. J Physiol 2007; 584: 305-312.