The effect of exercise on plasma soluble IL-6 receptor concentration: A dichotomous response

Exercise Immunology Review

Volumn 16, Issue , 2010, Pages 56-76

  Robson Ansley, Paula ^a   Cockburn, Emma ^a   Walshe, Ian ^a   Stevenson, Emma ^a   Nimmo, Myra ^b  

^a NORTHUMBRIA UNIVERSITY   (United Kingdom)

^b LOUGHBOROUGH UNIVERSITY   (United Kingdom)

Author keywords

DOMS; Eccentric exercise; Glycoprotein 130; Interleukin 6; sIL 6R; Soluble interleukin 6 receptor

Indexed keywords

GLYCOPROTEIN GP 130; INTERLEUKIN 6; INTERLEUKIN 6 RECEPTOR; PLASMA PROTEIN;

ADULT; BLOOD SAMPLING; CELL POPULATION; CENTRIFUGATION; CORRELATION ANALYSIS; DIET RESTRICTION; DYNAMOMETER; EXERCISE; EXERCISE RECOVERY; FROZEN SECTION; HAMSTRING; HUMAN; HUMAN EXPERIMENT; INFORMATION PROCESSING; KNEE FUNCTION; LABORATORY; LEUKOCYTE; MALE; MEDICAL LITERATURE; MEDICAL RESEARCH; MUSCLE FUNCTION; MUSCLE INJURY; NOCICEPTION; NORMAL HUMAN; PROTEIN BLOOD LEVEL; REGULATORY MECHANISM; REVIEW; SKELETAL MUSCLE; TISSUE INJURY; VELOCITY; VENOUS BLOOD; ARTICLE; BLOOD; INJURY; METABOLISM; PAIN; PAIN ASSESSMENT; PATHOPHYSIOLOGY; PHYSIOLOGY;

CYTOKINE RECEPTOR GP130; EXERCISE; HUMANS; INTERLEUKIN-6; MALE; MUSCLE, SKELETAL; PAIN; PAIN MEASUREMENT; RECEPTORS, INTERLEUKIN-6; YOUNG ADULT;

EID: 77957958068     PISSN: 10775552     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (94)

1. Adamopoulos S, Parissis J, Karatzas D, Kroupis C, Georgiadis M, Karavolias G, Paraskevaidis J, Koniavitou K, Coats AJS and Kremastinos DTh. Physical training modulates proinflammatory cytokines and the soluble fas/soluble fas ligand system in patients with chronic heart failure. Journal of the American College of Cardiology 39: 653-663, 2002. (Pubitemid 34158162)
2. Al Khalili L, Bouzakri K, Glund S, Lonnqvist F, Koistinen HA and Krook A. Signaling specificity of interleukin-6 action on glucose and lipid metabolism in skeletal muscle. Mol Endocrinol 20: 3364-3375, 2006. (Pubitemid 44833576)
3. Banks WA, Kastin AJ and Gutierrez EG. Penetration of interleukin-6 across the murine blood-brain barrier. Neurosci Lett 179: 53-56, 1994. (Pubitemid 24298557)
4. Best TM, Fiebig R, Corr DT, Brickson S and Ji L. Free radical activity, antioxidant enzyme, and glutathione changes with muscle stretch injury in rabbits. J Appl Physiol 87: 74-82, 1999. (Pubitemid 29330665)
5. Bishop NC, Gleeson M, Nicholas CW and Ali A. Influence of carbohydrate supplementation on plasma cytokine and neutrophil degranulation responses to high intensity intermittent exercise. Int J Sport Nutr Exerc Metab 12: 145-156, 2002.
6. Brozinick JT, Jr., Hawkins ED, Strawbridge AB and Elmendorf JS. Disruption of cortical actin in skeletal muscle demonstrates an essential role of the cytoskeleton in glucose transporter 4 translocation in insulin-sensitive tissues. J Biol Chem 279: 40699-40706, 2004. (Pubitemid 39287665)
7. Bruunsgaard H, Galbo H, Halkjaer-Kristensen J, Johansen TL, MacLean DA and Pedersen BK. Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage. J Physiol 499 (Pt 3): 833-841, 1997. (Pubitemid 27153602)
8. Byrne C and Eston R. The effect of exercise-induced muscle damage on isometric and dynamic knee extensor strength and vertical jump performance. J Sports Sci 20: 417-425, 2002. (Pubitemid 34516477)
9. 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 and 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 55: 2688-2697, 2006. (Pubitemid 44923666)
10. Chan MH, Carey AL, Watt MJ and Febbraio MA. Cytokine gene expression in human skeletal muscle during concentric contraction: evidence that IL-8, like IL-6, is influenced by glycogen availability.Am J Physiol Regul Integr Comp Physiol 287: R322-R327, 2004. (Pubitemid 38970283)
11. Cockburn E, Hayes PR, French DN, Stevenson E and St Clair GA. Acute milk-based protein-CHO supplementation attenuates exercise-induced muscle damage. Appl Physiol Nutr Metab 33: 775-783, 2008.
12. Collado-Hidalgo A, Bower JE, Ganz PA, Cole SW and Irwin MR. Inflammatory biomarkers for persistent fatigue in breast cancer survivors. Clin Cancer Res 12: 2759- 2766, 2006.
13. De Jongh RF, Vissers KC, Meert TF, Booij LH, De Deyne CS and Heylen RJ. The role of interleukin-6 in nociception and pain. Anesth Analg 96: 1096-103, table, 2003.
14. Depner CM, Gordon LK, Kidd JR and Miles MP. IL-6 bio-availability varies with basal CRP concentration and is unaffected by eccentric exercise. Med Sci Sports Exerc 40: S433, 2008.
15. Dimitrov S, Lange T, Benedict C, Nowell MA, Jones SA, Scheller J, Rose-John S and Born J. Sleep enhances IL-6 trans-signaling in humans. Faseb Journal 20: 2174-+, 2006.
16. Dziedzic T, Slowik A and Szczudlik A. Interleukin-6 and stroke: cerebral ischemia versus nonspecific factors influencing interleukin-6. Stroke 34: e229-e230, 2003.
17. Febbraio MA, Steensberg A, Keller C, Starkie RL, Nielsen HB, Krustrup P, Ott P, Secher NH and Pedersen BK. Glucose ingestion attenuates interlekin-6 release from contracting skeletal muscle in humans. J Physiol 549: 607-612, 2003. (Pubitemid 36701770)
18. Febbraio MA, Hiscock N, Sacchetti M, Fischer CP and Pedersen BK. Interleukin-6 is a novel factor mediating glucose homeostatis during skeletal muscle contraction. Diabetes 53: 1643-1648, 2004. (Pubitemid 38864744)
19. Frieling JM, van Deuren JW, van der Meer CC, Visser M and Sauerwein RW. Circulating interleukin-6 receptor in patients with sepsis syndrome. J Infection 171: 469-472, 1995.
20. Gaillard J, Pugniere M, Tresca J, Mani J, Klein B and Brochier J. Interleukin-6 receptor signaling. II. Bio-availability of interleukin-6 in serum. Eur Cytokine Netw 10: 337-344, 1999.
21. Geiger PC, Hancock C, Wright DC, Han DH and Holloszy JO. IL-6 increases muscle insulin sensitivity only at superphysiological levels. Am J Physiol Endocrinol Metab 292: E1842-E1846, 2007. (Pubitemid 47084722)
22. Glund S, Treebak JT, Long YC, Barres R, Viollet B, Wojtaszewski JF and Zierath JR. Role of adenosine 5′-monophosphate-activated protein kinase in interleukin-6 release from isolated mouse skeletal muscle. Endocrinology 150: 600-606, 2009.
23. Gray SR, Baker G, Wright A, Fitzsimons CF, Mutrie N and Nimmo MA. The effect of a 12 week walking intervention on markers of insulin resistance and systemic inflammation. Prev Med 48: 39-44, 2009.
24. Gray SR, Clifford M, Lancaster R, Leggate M, Davies M and Nimmo MA. The response of circulating levels of the interleukin-6/interleukin-6 receptor complex to exercise in young men. Cytokine 47: 98-102, 2009.
25. Gray SR, Ratkevicius A, Wackerhage H, Coats P and Nimmo MA. The effect of interleukin-6 and the interleukin-6 receptor on glucose transport in mouse skeletal muscle. Exp Physiol 94: 899-905, 2009.
26. Gray SR, Robinson M and Nimmo MA. Response of plasma IL-6 and its soluble receptors during submaximal exercise to fatigue in sedentary middle-aged men. Cell Stress Chaperones 2008.
27. Halson SL, Lancaster GI, Jeukendrup AE and Gleeson M. Immunological responses to overreaching in cyclists. Med Sci Sports Exerc 35: 854-861, 2003. (Pubitemid 36547390)
28. Harrison AJ and Gaffney SD. Effects of muscle damage on stretch-shortening cycle function and muscle stiffness control. J Strength Cond Res 18: 771-776, 2004. (Pubitemid 39627317)
29. Hikida RS, Staron RS, Hagerman FC, Sherman WM and Costill DL. Muscle fiber necrosis associated with human marathon runners. J Neurol Sci 59: 185-203, 1983. (Pubitemid 13113561)
30. Hurst SM, Wilkinson TS, McLoughlin RM, Jones S, Horiuchi S, Yamamoto N, Rose-John S, Fuller GM, Topley N and Jones SA. Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation. Immunity 14: 705-714, 2001. (Pubitemid 32592418)
31. Inagaki M, Isono M, Okuyama T, Sugawara Y, Akechi T, Akizuki N, Fujimori M, Mizuno M, Shima Y, Kinoshita H and Uchitomi Y. Plasma interleukin-6 and fatigue in terminally ill cancer patients. J Pain Symptom Manage 35: 153-161, 2008.
32. Jones SA, Horiuchi S, Novick D,Yamamoto N and Fuller GM. Shedding of the soluble IL-6 receptor is triggered by Ca2+ mobilization, while basal release is predominantly the product of differential mRNA splicing in THP-1 cells. Eur J Immunol 28: 3514-3522, 1998. (Pubitemid 28510762)
33. Jones SA, Horiuchi S, Topley N, Yamamoto N and Fuller GM. The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J 15: 43-58, 2001. (Pubitemid 32061655)
34. Jones SA, Novick D, Horiuchi S,Yamamoto N, Szalai AJ and Fuller GM. C-reactive protein: a physiological activator of interleukin 6 receptor shedding. J Exp Med 189: 599-604, 1999. (Pubitemid 29187382)
35. Jonsdottir IH, Schjerling P, Ostrowski K, Asp S, Richter EA and Pedersen BK. Muscle contractions induce interleukin-6 mRNA production in rat skeletal muscles. J Physiol 528 Pt 1: 157-163, 2000.
36. Jostock T, Mullberg J, Ozbek S, Atreya R, Blinn G, Voltz N, Fischer M, Neurath MF and Rose-John S. Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses. Eur J Biochem 268: 160-167, 2001. (Pubitemid 32052260)
37. Keller C, Steensberg A, Hansen AK, Fischer CP, Plomgaard P and Pedersen BK. Effect of exercise, training, and glycogen availability on IL-6 receptor expression in human skeletal muscle. J Appl Physiol 99: 2075-2079, 2005. (Pubitemid 41691622)
38. Keller C, Steensberg A, Pilegaard H, Osada T, Saltin B, Pedersen BK and Neufer PD. Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen content. FASEB 15: 2748-2750, 2001.
39. Keller P, Penkowa M, Keller C, Steensberg A, Fischer CP, Giralt M, Hidalgo J and Pedersen BK. Interleukin-6 receptor expression in contracting human skeletal muscle: regulating role of IL-6. FASEB J 19: 1181-1183, 2005. (Pubitemid 40946458)
40. Kelly M, Keller C,Avilucea PR, Keller P, Luo Z, Xiang X, Giralt M, Hidalgo J, Saha AK, Pedersen BK and Ruderman NB. AMPK activity is diminished in tissues of IL-6 knockout mice: the effect of exercise. Biochem Biophys Res Commun 320: 449-454, 2004. (Pubitemid 38798888)
41. Kishimoto T. The biology of interleukin-6. Blood 74: 1-10, 1989. (Pubitemid 19187402)
42. Kordula T, Rokita H, Koj A, Fiers W, Gauldie J and Baumann H. Effects of interleukin-6 and leukemia inhibitory factor on the acute phase response and DNA synthesis in cultured rat hepatocytes. Lymphokine Cytokine Res 10: 23-26, 1991.
43. Lowe DA, Warren GL, Ingalls CP, Boorstein DB and Armstrong RB. Muscle function and protein metabolism after initiation of eccentric contraction-induced injury. J Appl Physiol 79: 1260-1270, 1995.
44. MacIntyre DL, Sorichter S, Mair J, Berg A and McKenzie DC. Markers of inflammation and myofibrillar proteins following eccentric exercise in humans. Eur J Appl Physiol 84: 180-186, 2001. (Pubitemid 32229391)
45. Merrill GF, Kurth EJ, Hardie DG and Winder WW. AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am J Physiol 273: E1107-E1112, 1997.
46. Miles MP, Andring JM, Pearson SD, Gordon LK, Kasper C, Depner CM and Kidd JR. Diurnal variation, response to eccentric exercise, and association of inflammatory mediators with muscle damage variables. J Appl Physiol 104: 451-458, 2008. (Pubitemid 351231492)
47. Modur V, Li Y, Zimmerman GA, Prescott SM and McIntyre TM. Retrograde inflammatory signaling from neutrophils to endothelial cells by soluble interleukin-6 receptor alpha. J Clin Invest 100: 2752-2756, 1997. (Pubitemid 28007543)
48. Mullberg J, Schooltink H, Stoyan T, Heinrich PC and Rose-John S. Protein kinase C activity is rate limiting for shedding of the interleukin-6 receptor. Biochem Biophys Res Commun 189: 794-800, 1992. (Pubitemid 23032443)
49. Musi N and Goodyear LJ. AMP-activated protein kinase and muscle glucose uptake. Acta Physiol Scand 178: 337-345, 2003. (Pubitemid 36960424)
50. Nieman DC, Nehlsen-Cannarella SL, Fagoaga OR, Henson DA, Utter A, Davis JM, Williams F and Butterworth DE. Influence of mode and carbohydrate on the cytokine response to heavy exertion. Med Sci Sports Exerc 30: 671-678, 1998. (Pubitemid 28210989)
51. Nishimoto N, Kishimoto T and Yoshizaki K. Anti-interleukin 6 receptor antibody treatment in rheumatic disease. Ann Rheum Dis 59 Suppl 1: i21-i27, 2000.
52. Nishimoto N, Sasai M, Shima Y, Nakagawa M, Matsumoto T, Shirai T, Kishimoto T and Yoshizaki K. Improvement in Castleman's disease by humanized anti-interleukin-6 receptor antibody therapy. Blood 95: 56-61, 2000. (Pubitemid 30017224)
53. Nosaka K, Newton M and Sacco P. Delayed-onset muscle soreness does not reflect the magnitude of eccentric exercise-induced muscle damage. Scand J Med Sci Sports 12: 337-346, 2002.
54. Obreja O, Schmelz M, Poole S and Kress M. Interleukin-6 in combination with its soluble IL-6 receptor sensitises rat skin nociceptors to heat, in vivo. Pain 96: 57-62, 2002. (Pubitemid 34270628)
55. Paonessa G, Graziani R, De SA, Savino R, Ciapponi L, LahmA, Salvati AL, Toniatti C and Ciliberto G. Two distinct and independent sites on IL-6 trigger gp 130 dimer formation and signalling. EMBO J 14: 1942-1951, 1995.
56. Parry-Billings M, Budgett R, Koutedakis Y, Blomstrand E, Brooks S, Williams C, Calder PC, Pilling S, Baigrie R and Newsholme EA. Plasma amino acid concentrations in the overtraining syndrome: possible effects on the immune system. Med Sci Sports Exerc 24: 1353-1358, 1992. (Pubitemid 23006956)
57. Patarca M, Garcia M,Walters M, Dombroski D, Pons H and Fletcher M. Dysregulated expression of soluble immune mediator receptrs in a subset of patients with Chronic Fatigue syndrome. Journal of Chronic Fatigue syndrome 1: 81-96, 1994.
58. Patterson S, Reid S, Gray S and Nimmo M. The response of plasma interleukin-6 and its soluble receptors to exercise in the cold in humans. Journal of Sports Science 26: 927-933, 2008. (Pubitemid 351935663)
59. Pedersen BK. Edward F. Adolph Distinguished Lecture: Muscle as an Endocrine Organ: IL-6 and other myokines. J Appl Physiol 2009.
60. Pedersen BK, Bruunsgaard H, Klokker M, Kappel M, MacLean DA, Nielsen HB, Rohde T, Ullum H and Zacho M. Exercise-induced immunomodulation - possible roles of neuroendocrine and metabolic factors. Int J Sports Med 18 Suppl 1: S2-S7, 1997.
61. Pedersen BK, Steensberg A and Schjerling P. Muscle-derived interleukin-6: possible biological effects. J Physiol 536: 329-337, 2001. (Pubitemid 32976115)
62. Peters M, Jacobs S, Ehlers M, Vollmer P, Mullberg J, Wolf E, Brem G, Meyer zum Buschenfelde KH and Rose-John S. The function of the soluble interleukin 6 (IL-6) receptor in vivo: sensitization of human soluble IL-6 receptor transgenic mice towards IL-6 and prolongation of the plasma half-life of IL-6. J Exp Med 183: 1399-1406, 1996. (Pubitemid 26134283)
63. Robinson M, Gray SR, Watson MS, Kennedy G, Hill A, Belch JJ and Nimmo MA. Plasma IL-6, its soluble receptors and F-isoprostanes at rest and during exercise in chronic fatigue syndrome. Scand J Med Sci Sports 2009.
64. Robson P. Elucidating the unexplained underperformance syndrome in endurance athletes : the interleukin-6 hypothesis. Sports Med 33: 771-781, 2003. (Pubitemid 36995258)
65. Robson-Ansley P, de Milander L, Collins M and Noakes TD. Acute interleukin-6 administration does not alter plasma soluble interleukin-6 receptor concentration following an acute bout of exercise. 11th Annual Congress of the European College of Sport Science P33, 2006.
66. Robson-Ansley P, Barwood M, Canavan J, Hack S, Eglin C, Davey S, Hewitt J, Hull J and Ansley L. The effect of repeated endurance exercise on IL-6 and sIL-6R and their relationship with sensations of fatigue at rest. Cytokine 45: 111-116, 2009.
67. Robson-Ansley P, Barwood M, Eglin C and Ansley L. The effect of carbohydrate ingestion on the interleukin-6 response to a 90-minute run time trial. Int J Sports Physiol Perform 4: 186-194, 2009.
68. Robson-Ansley PJ, Blannin A and Gleeson M. Elevated plasma interleukin-6 levels in trained male triathletes following an acute period of intense interval training. Eur J Appl Physiol 99: 353-360, 2007. (Pubitemid 46218505)
69. Robson-Ansley PJ, de Milander L, Collins M and Noakes TD. Acute interleukin-6 administration impairs athletic performance in healthy, trained male runners. Can J Appl Physiol 29: 411-418, 2004. (Pubitemid 39107948)
70. Sacheck JM, Cannon JG, Hamada K, Vannier E, Blumberg JB and Roubenoff R. Age-related loss of associations between acute exercise-induced IL-6 and oxidative stress. Am J Physiol Endocrinol Metab 291: E340-E349, 2006. (Pubitemid 44035294)
71. Schobitz B, Pezeshki G, Pohl T, Hemmann U, Heinrich PC, Holsboer F and Reul JM. Soluble interleukin-6 (IL-6) receptor augments central effects of IL-6 in vivo. FASEB J 9: 659-664, 1995.
72. Schobitz B, Voorhuis DA and de Kloet ER. Localization of interleukin 6 mRNA and interleukin 6 receptor mRNA in rat brain. Neurosci Lett 136: 189-192, 1992.
73. Semark A, Noakes TD, St Clair GA and Lambert MI. The effect of a prophylactic dose of flurbiprofen on muscle soreness and sprinting performance in trained subjects. J Sports Sci 17: 197-203, 1999. (Pubitemid 29231909)
74. Silverman NE, Nicklas BJ and Ryan AS. Addition of aerobic exercise to a weight loss program increases BMD, with an associated reduction in inflammation in overweight postmenopausal women. Calcif Tissue Int 84: 257-265, 2009.
75. Smith LL. Cytokine hypothesis of overtraining: a physiological adaptation to excessive stress? Med Sci Sports Exerc 32: 317-331, 2000. (Pubitemid 30108110)
76. Sommer C and Kress M. Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett 361: 184-187, 2004. (Pubitemid 38609247)
77. Sorichter S, Puschendorf B and Mair J. Skeletal muscle injury induced by eccentric muscle action: muscle proteins as markers of muscle fiber injury. Exerc Immunol Rev 5: 5-21, 1999. (Pubitemid 29340639)
78. Spath-Schwalbe E, Hansen K, Schmidt F, Schrezenmeier H, Marshall L, Burger K, Fehm HL and Born J. Acute effects of recombinant human interleukin-6 on endocrine and central nervous sleep functions in healthy men. J Clin Endocrinol Metab 83: 1573-1579, 1998. (Pubitemid 28501024)
79. Starkie RL,Arkinstall MJ, Koukoulas I, Hawley JA and Febbraio MA. Carbohydrate ingestion attenuates the increase in plasma interleukin-6, but not skeletal muscle interleukin-6 mRNA, during exercise in humans. J Physiol 533: 585-591, 2001. (Pubitemid 32520010)
80. Steensberg A, Febbraio MA, Osada T, Schjerling P, van Hall G, Saltin B and Pedersen BK. Il-6 production in contracting human skeletal muscle is influenced by preexercise muscle glycogen content. J Physiol 537: 633-639, 2001. (Pubitemid 33130517)
81. Steensberg A, van Hall G, Osada T, Sacchetti M, Saltin B and Klarlund PB. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol 529 Pt 1: 237-242, 2000.
82. Suzuki K, Nakaji S, Yamada M, Totsuka M, Sato K and Sugawara K. Systemic inflammatory response to exhaustive exercise. Cytokine kinetics. Exerc Immunol Rev 8: 6-48, 2002.
83. Taga T and Kishimoto T. Gp130 and the interleukin-6 family of cytokines.Annu Rev Immunol 15: 797-819, 1997. (Pubitemid 27169299)
84. Twist C and Eston R. The effects of exercise-induced muscle damage on maximal intensity intermittent exercise performance. Eur J Appl Physiol 94: 652-658, 2005. (Pubitemid 41136067)
85. Ueda K, Takahashi M, Ozawa K and Kinoshita M. Decreased soluble interleukin-6 receptor in patients with acute myocardial infarction. Am Heart J 138: 908-915, 1999. (Pubitemid 29523278)
86. van Hall G, Sacchetti M, Radegran G and Saltin B. Human skeletal muscle fatty acid and glycerol metabolism during rest,exercise and recovery. Journal of Physiology 543.3: 1047-1058, 2002.
87. Vermes C, Jacobs JJ, Zhang J, Firneisz G, Roebuck KA and Glant TT. Shedding of the interleukin-6 (IL-6) receptor (gp80) determines the ability of IL-6 to induce gp130 phosphorylation in human osteoblasts. J Biol Chem 277: 16879-16887, 2002. (Pubitemid 34967713)
88. Walshe I, Ansley L and Robson-Ansley P. Carbohydrate supplementation does not alter the plasma soluble gp130 concentration in response to prolonged running. 9th Symposium of the International Society of Exercise and Immunology 103, 2009.
89. Weigert C, Hennige AM, Brodbeck K, Haring HU and Schleicher ED. Interleukin-6 acts as insulin sensitizer on glycogen synthesis in human skeletal muscle cells by phosphorylation of Ser473 of Akt. Am J Physiol Endocrinol Metab 289: E251-E257, 2005. (Pubitemid 41076625)
90. Yamashiki M, Kosaka Y, Nishimura A,Watanabe S, Nomoto M and Ichida F. Analysis of serum cytokine levels in primary biliary cirrhosis patients and healthy adults. J Clin Lab Anal 12: 77-82, 1998. (Pubitemid 28113671)
91. Yokoyama A, Kohno N, Sakai K, Kondo K, Hirasawa Y and Hiwada K. Circulating levels of soluble interleukin-6 receptor in patients with bronchial asthma. Am J Respir Crit Care Med 156: 1688-1691, 1997. (Pubitemid 27505543)
92. You T, Berman DM, Ryan AS and Nicklas BJ. Effects of hypocaloric diet and exercise training on inflammation and adipocyte lipolysis in obese postmenopausal women. Journal of clinical endocrinology and metabolism 89: 1793-1746, 2004.
93. Zohlnhofer D, Graeve L, Rose-John S, Schooltink H, Dittrich E and Heinrich PC. The hepatic interleukin-6 receptor. Down-regulation of the interleukin-6 binding subunit (gp80) by its ligand. FEBS Lett 306: 219-222, 1992.
94. Leggate M, Nowell MA, Jones SA and Nimmo, MA (2010) The response of interleukin-6 and soluble interleukin-6 receptor isoforms following intermittent high intensity and continuous moderate intensity cycling. Cell Stress & Chaperones DOI 10.1007/s12192-010-0192-z