Download PDF
Int J Sports Med 2008; 29(2): 102-109
DOI: 10.1055/s-2007-965115
Physiology & Biochemistry

© Georg Thieme Verlag KG Stuttgart · New York

Resistive Exercise Blunts LPS-stimulated TNF-α and Il-1β

M. D. Phillips1 , M. G. Flynn2 , B. K. McFarlin3 , L. K. Stewart4 , K. L. Timmerman2 , H. Ji5
  • 1Department of Kinesiology, Texas Christian University, Fort Worth, TX, United States
  • 2Wastl Human Performance Lab, Purdue University, West Lafayette, IN, United States
  • 3Health and Human Performance, University of Houston, Houston, TX, United States
  • 4Department of Kinesiology, Louisiana State University, Baton Rouge, LA, United States
  • 5Department of Basic and Medical Sciences, Second Military University, Shanghai, China
Further Information

Publication History

accepted after revision December 15, 2006

Publication Date:
13 September 2007 (online)

Also available at
    Permissions and Reprints

Abstract

To examine the influence of acute resistive exercise and “hormone status” on cytokine profile, 35 postmenopausal women (72 ± 6.2 yr) underwent a moderate-high-intensity resistive exercise bout or rested. There were 4 groups: no hormone replacement (NHR, n = 9), hormone replacement (HRT, n = 12), selective estrogen receptor modulator (SER, n = 7), or resting control (no hormone replacement, CON, n = 7). NHR, HRT, and SER exercised (3 sets, 10 exercises @ 80 % 1RM). Blood was collected pre-exercise (PR), postexercise (PO), and two hours (2H) postexercise (same times for CON). Blood was diluted 1 : 10 in culture medium and incubated (37 °C, 5 % CO2, 24 h) with lipopolysaccharide (LPS, 25 µg · ml-1). Serum and supernatant from LPS-stimulated blood were analyzed for IL-6, IL-1β, and TNF-α using ELISA. Resistive exercise increased PO serum IL-6, and PO LPS-stimulated IL-6 and IL-1β in the exercise groups (HRT, NHR, SER collapsed; EX, n = 28). LPS-stimulated IL-1β remained elevated at 2H in EX and was significantly higher than PR in CON at 2H. Expressed per monocyte, EX had significantly lower IL-1β and TNF-α LPS-stimulated production at PO and 2H compared to CON, indicating an exercise-induced blunting of an apparent diurnal response on cytokine production. In postmenopausal women, acute resistive exercise increased circulating IL-6, but reversed an apparent diurnal increase in LPS-stimulated IL-1β and TNF-α production with no influence of hormone replacement or raloxifene.

Key words

interleukin‐6 (IL‐6) - raloxifene - postmenopausal women - inflammatory cytokine

References

  • 1 Abrahamsen B, Stilgren L S, Rettmer E, Bonnevie-Nielsen V, Beck-Nielsen H. Effects of the natural and artificial menstrual cycle on the production of osteoprotegerin and the bone resorptive cytokines IL-1β and IL‐6.  Calcif Tissue Int. 2003;  72 18-23
    CrossrefPubMedGoogle Scholar
  • 2 Berg G, Ekerfelt C, Hammar M, Lindgren R, Mathiesen L, Ernerudh J. Cytokine changes in postmenopausal women treated with estrogens: a placebo-controlled study.  Am J Reprod Immunol. 2002;  48 63-69
    CrossrefPubMedGoogle Scholar
  • 3 Bruunsgaard H, Pedersen A N, Schroll M, Skinhoj P, Pedersen B K. Impaired production of proinflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in elderly humans.  Clin Exp Immunol. 1999;  118 235-241
    CrossrefPubMedGoogle Scholar
  • 4 Carrasco D I, Delp M D, Ray C A. Effect of concentric and eccentric muscle actions on muscle sympathetic nerve activity.  J Appl Physiol. 1999;  86 558-563
    PubMedGoogle Scholar
  • 5 Cheung J, Mak Y T, Papaioannou S, Evans B AJ, Fogelman I, Hampson G. Interleukin-6 (IL‐6), IL‐1, receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin production by human osteoblastic cells: comparison of the effects of 17-beta oestradiol and raloxifene.  J Endocrinol. 2003;  177 423-433
    CrossrefPubMedGoogle Scholar
  • 6 Cohen-Solal M E, Graulet A M, Gueris J, Denne M A, Bergot C, Morieux C, Sedel L, Kuntz D, DeVernejoul M C. Bone resorption at the femoral neck is dependent on local factors in nonosteoporotic late postmenopausal women: an in vitro-in vivo study.  J Bone Mineral Res. 1995;  10 307-314
    PubMedGoogle Scholar
  • 7 Delpedro A D, Barjavel M J, Mamdouh Z, Faure S, Bakouche O. Signal transduction in LPS-activated aged and young monocytes.  J Interferon Cytokine Res. 1998;  18 429-437
    PubMedGoogle Scholar
  • 8 DeRijk R, Michelson D, Karp B, Petrides J, Galliven E, Deuster P, Paciotti G, Gold P W, Sternberg E M. Exercise and circadian rhythm-induced variations in plasma cortisol differentially regulate interleukin-1β (IL-1β), IL‐6, and tumor necrosis factor-σ (TNF-σ) production in humans: high sensitivity of TNF-σ and resistance of IL‐6.  J Clin Endocrinol Metab. 1997;  82 2182-2191
    CrossrefPubMedGoogle Scholar
  • 9 Devaraj S, O'Keefe G, Jialal I. Defining the proinflammatory phenotype using high sensitivity C-reactive protein levels as the biomarker.  J Clin Endocrinol Metab. 2005;  90 4549-4554
    CrossrefPubMedGoogle Scholar
  • 10 Drenth J P, Krebbers R J, Bijzet J, van der Meer J W. Increased circulating cytokine receptors and ex vivo interleukin-1 receptor antagonist and interleukin1β production but decreased tumour necrosis factor-α production after a 5-km run.  Eur J Clin Invest. 1998;  28 866-872
    CrossrefPubMedGoogle Scholar
  • 11 Fatouros I G, Kambas A, Katrabasas I, Nikolaidis K, Chatzinikolaou A, Leontsini D, Taxildaris K. Strength training and detraining effects on muscular strength, anaerobic power, and mobility of inactive older men are intensity dependent.  Br J Sports Med. 2005;  39 776-780
    CrossrefPubMedGoogle Scholar
  • 12 Fatouros I G, Kambas A, Katrabasas I, Leontsini D, Chatzinikolaou A, Jamurtas A Z, Douroudos I, Nggelousis N, Taxildaris K. Resistance training and detraining effects on flexibility performance in the elderly are intensity-dependent.  J Strength Cond Res. 2006;  20 634-642
    CrossrefPubMedGoogle Scholar
  • 13 Fiatarone M A, Marks E C, Ryan N D, Meredith C N, Lipsitz L A, Evans W J. High-intensity strength training in nonagenarians. Effects on skeletal muscle.  JAMA. 1990;  263 3029-3034
    CrossrefPubMedGoogle Scholar
  • 14 Flynn M G, McFarlin B K, Phillips M D, Stewart L K, Timmerman K L. Toll-like receptor 4 and CD 14 mRNA expression are lower in resistive exercise-trained elderly women.  J Appl Physiol. 2003;  95 1833-1842
    PubMedGoogle Scholar
  • 15 Gabriel P, Cakman I, Rink L. Overproduction of monokines by leukocytes after stimulation with lipopolysaccharide in the elderly.  Exp Gerontol. 2002;  37 235-247
    CrossrefPubMedGoogle Scholar
  • 16 Greiwe J S, Cheng B, Rubin D C, Yarasheski K E, Semenkovich C F. Resistance exercise decreases skeletal muscle tumor necrosis factor α in frail elderly humans.  FASEB. 2001;  15 475-482
    CrossrefPubMedGoogle Scholar
  • 17 Haff G G, Koch A J, Potteiger J A, Kuphal K E, Magee L M, Green S B, Jakicic J J. Carbohydrate supplementation attenuates muscle glycogen loss during acute bouts of resistance exercise.  Int J Sport Nutr Exerc Metab. 2000;  10 326-339
    CrossrefPubMedGoogle Scholar
  • 18 Helge J W, Stallknecht B, Pedersen B K, Galbo H, Kiens B, Richter E A. The effect of graded exercise on IL‐6 release and glucose uptake in human skeletal muscle.  J Physiol. 2003;  546 299-305
    CrossrefPubMedGoogle Scholar
  • 19 Kalapotharakos V I, Michalopoulou M, Godolias G, Tokmakidis S P, Malliou P V, Gourgoulis V. The effects of high- and moderate-resistance training on muscle function in the elderly.  J Aging Phys Activity. 2004;  11 131-143
    PubMedGoogle Scholar
  • 20 Martin Ginis K A, Latimer A E, Brawley L R, Jung M E, Hicks A L. Weight training to activities of daily living: helping older adults make a connection.  Med Sci Sports Exerc. 2006;  38 116-121
    CrossrefPubMedGoogle Scholar
  • 21 Muzio M, Bosisio D, Polentarutti N, D'amico G, Stoppacciao A, Mancinelli R, van't Veer C, Penton-Rol G, Ruco L P, Allavena P, Mantovaani A. Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dentritic cells.  J Immunol. 2000;  164 5998-6004
    PubMedGoogle Scholar
  • 22 Makkonen N, Salminen A, Rogers M J, Frith J C, Urtti A, Azhayeva E, Mönkkönen J. Contrasting effects of alendronate and clodronate on RAW 264 macrophages: the role of a bisphosphonate metabolite.  Eur J Pharm Sci. 1999;  8 109-118
    PubMedGoogle Scholar
  • 23 Moldoveanu A I, Shephard R J, Shek P N. Exercise elevates plasma levels but not gene expression of IL-1β, IL‐6, and TNF-α in blood mononuclear cells.  J Appl Physiol. 2000;  89 1499-1504
    PubMedGoogle Scholar
  • 24 Nilsson J, Jovinge S, Neimann A, Reneland R, Lithell H. Relation between plasma tumor necrosis factor-alpha and insulin sensitivity in elderly men with non-insulin-dependent diabetes mellitus.  Arterioscler Thromb Vasc Biol. 1998;  18 1199-1202
    CrossrefPubMedGoogle Scholar
  • 25 Ostrowski K, Hermann C, Bangash A, Schjerling P, Nielsen J N, Pedersen B K. A trauma-like elevation of plasma cytokines in humans in response to treadmill running.  J Physiol. 1998;  513 889-894
    CrossrefPubMedGoogle Scholar
  • 26 Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen B K. Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans.  J Physiol. 1999;  515 287-291
    CrossrefPubMedGoogle Scholar
  • 27 Pacifici R, Vannice J L, Rifas L, Kimble R B. Monocytic secretion of interleukin-1 receptor antagonist in normal and osteoporotic women: effects of menopause and estrogen/progesterone therapy.  J Clin Endocrinol Metab. 1993;  77 1135-1141
    CrossrefPubMedGoogle Scholar
  • 28 Papadopoulos N G, Georganas K, Skoutellas V, Konstantellos E, Lyritis G P. Correlation of interleukin-6 serum levels with bone density in postmenopausal women.  Clin Rheumatology. 1997;  16 162-165
    PubMedGoogle Scholar
  • 29 Papanicolaou D A, Petrides J S, Tsigos C, Bina S, Kalogeras K T, Wilder R, Gold P W, Deuster P A, Chrousos G P. Exercise stimulates interleukin-6 secretion: inhibition by glucocorticoids and correlation with catecholamines.  Am J Physiol. 1996;  271 E601-E605
    PubMedGoogle Scholar
  • 30 Pedersen B K, Bruunsgaard H. Possible beneficial role of exercise in modulating low-grade inflammation in the elderly.  Scand J Med Sci Sports. 2003;  13 56-62
    CrossrefPubMedGoogle Scholar
  • 31 Pedersen B K, Steensberg A, Fischer C, Keller C, Keller P, Plomgaard P, Febbraio M, Saltin B. Searching for the exercise factor: is IL‐6 a candidate?.  J Muscle Res Cell Motil. 2003;  24 113-119
    CrossrefPubMedGoogle Scholar
  • 32 Pottratz S T, Bellido T, Mocharla H, Crabb D, Manologas S C. 17-beta estradiol inhibits expression of human interleukin-6 promoter-reporter constructs by a receptor-dependent mechanism.  J Clin Invest. 1994;  93 944-950
    PubMedGoogle Scholar
  • 33 Rachon D, Mysliwska J, Suchecka-Rachon K, Wieckiewicz J, Mysliwski A. Effects of oestrogen deprivation on interleukin-6 production by peripheral blood mononuclear cells of postmenopausal women.  J Endocrinol. 2002;  172 387-395
    CrossrefPubMedGoogle Scholar
  • 34 Rhind S G, Castellani J W, Brenner I KM, Shephard R J, Zamecnik J, Montain S J, Young A J, Shek P N. Intracellular monocyte and serum cytokine expression is modulated by exhausting exercise and cold exposure.  Am J Physiol. 2001;  281 R66-R75
    PubMedGoogle Scholar
  • 35 Rogers A, Eastell R. The effect of 17β-estradiol on production of cytokines in cultures of peripheral blood.  Bone. 2001;  29 30-34
    CrossrefPubMedGoogle Scholar
  • 36 Ross R. Atherosclerosis is an inflammatory disease.  Am Heart J. 1999;  138 S419-S420
    CrossrefPubMedGoogle Scholar
  • 37 Sabroe I, Jones E C, Usher L R, Whyte M KB, Dower S K. Toll-like receptor (TLR)2 and TLR4 in human peripheral blood granulocytes: a critical role for monocytes in leukocyte lipopolysaccharide responses.  J Immunol. 2002;  168 4701-4710
    PubMedGoogle Scholar
  • 38 Smith J K, Dykes R, Douglas J E, Krishnaswamy G, Berk S. Long-term exercise and atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease.  JAMA. 1999;  281 1722-1727
    CrossrefPubMedGoogle Scholar
  • 39 Smith L L, Anwar A, Fragen M, Rananto C, Johnson R, Holbert D. Cytokines and cell adhesion molecules associated with high-intensity eccentric exercise.  Eur J Appl Physiol. 2000;  82 61-67
    CrossrefPubMedGoogle Scholar
  • 40 Starkie R L, Rolland J, Angus D J, Anderson M J, Febbraio M A. Circulating monocytes are not the source of elevations in plasma IL‐6 and TNF-α levels after prolonged running.  Am J Physiol. 2000;  280 C769-C774
    PubMedGoogle Scholar
  • 41 Steensberg A, van Hall G, Osada T, Sacchetti M, Saltin B, Pedersen B K. 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
    CrossrefPubMedGoogle Scholar
  • 42 Steensberg A, Febbraio M A, Osada T, Schjerling P, van Hall G, Saltin B, Pedersen B K. Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content.  J Physiol. 2001;  537 633-639
    CrossrefPubMedGoogle Scholar
  • 43 Stouthard J M, Romijn J A, van Der P T, Endert E, Klein S, Bakker P J, Veenhof C H, Sauerwein H P. Endocrinologic and metabolic effects of interleukin-6 in humans.  Am J Physiol. 1995;  268 E813-E819
    PubMedGoogle Scholar
  • 44 Stouthard J ML, Oude Elferink R PJ, Sauerwein H P. Interleukin-6 enhances glucose transport in 3T3-L1 adipocytes.  Biochem Bioph Res Co. 1996;  220 241-245
    CrossrefPubMedGoogle Scholar
  • 45 Suarez E C, Boyle S H, Lewis J G, Hall R P, Young K H. Increases in stimulated secretion of proinflammatory cytokines by blood monocytes following arousal of negative affect: the role of insulin resistance as a moderator.  Brain Behav Immun. 2006;  20 331-338
    CrossrefPubMedGoogle Scholar
  • 46 Taranta A, Brama M, Teti A, De luca V, Scandurra R, Spera G, Agnusd D, Termine J D, Migliaccio S. The selective estrogen receptor modulator raloxifene regulates osteoclast and osteoblast activity in vitro.  Bone. 2002;  30 368-376
    CrossrefPubMedGoogle Scholar
  • 47 Teranishi C T, Flynn M G, Phillips M D, Liu J, Horrall M. The effects of resistance training on peripheral blood cytokine production in women aged 18 - 39 and 65 - 79 yr (Abstract).  Med Sci Sports Exerc. 2001;  33 S78
    PubMedGoogle Scholar
  • 48 Toft A D, Jensen L B, Bruunsgaard H, Ibfelt T, Halkjaer-Kristensen J, Febbraio M, Pedersen B K. Cytokine response to eccentric exercise in young and elderly humans.  Am J Physiol. 2002;  283 C289-C295
    PubMedGoogle Scholar
  • 49 van Hall G, Steensberg A, Sacchetti M, Fischer C, Keller C, Schjerling P, Hiscock N, Moller K, Saltin B, Febbraio M A, Pedersen B K. Interleukin-6 stimulates lipolysis and fat oxidation in humans.  J Clin Endocrinol Metab. 2003;  88 3005-3010
    CrossrefPubMedGoogle Scholar
  • 50 Viereck V, Grundker C, Blaschke S, Niederkleine B, Siggelkow H, Frosch K H, Raddatz D, Emons G, Hofbauer L C. Raloxifene concurrently stimulates osteoprotegerin and inhibits interleukin-6 production by human trabecular osteoblasts.  J Clin Endocrinol Metab. 2003;  88 4206-4213
    CrossrefPubMedGoogle Scholar
  • 51 Weinstock C, Konig D, Harnischmacher R, Keul J, Berg A, Northoff H. Effect of exhaustive exercise stress on the cytokine response.  Med Sci Sports Exerc. 1997;  29 345-354
    PubMedGoogle Scholar

Dr. PhD Melody D. Phillips

Department of Kinesiology
Texas Christian University

TCU Box 297730, 3005 Stadium Dr.

Fort Worth, TX 76123

United States

Phone: + 1 81 72 57 68 65

Fax: + 1 81 72 57 77 02

Email: m.phillips@tcu.edu

      >