Skip to main content
Log in

Exhaustive exercise causes an anti-inflammatory effect in skeletal muscle and a pro-inflammatory effect in adipose tissue in rats

  • Original Article
  • Published:
European Journal of Applied Physiology Aims and scope Submit manuscript

Abstract

It is well known that exhaustive exercise increases serum and skeletal muscle IL-6 concentrations. However, the effect of exhaustive exercise on the concentrations of other cytokines in the muscle and in the adipose tissue is controversial. The purpose of this study was to evaluate the effect of exhaustive exercise on mRNA and protein expression of IL-10, TNF-α and IL-6 in different types of skeletal muscle (EDL, soleus) and in two different depots of white adipose tissue (mesenteric–MEAT and retroperitoneal–RPAT). Rats were killed by decapitation immediately (E0 group, n = 6), 2 (E2 group, n = 6) and 6 (E6 group, n = 6) hours after the exhaustion protocol, which consisted of running on a treadmill (approximately 70% VO2max for 50 min and then subsequently at an elevated rate that increased at 1 m/min every minute, until exhaustion). The control group (C group, n = 6) was not subjected to exercise. Cytokine protein expression increased in EDL, soleus, MEAT and RPAT from all exercised groups, as detected by ELISA. EDL IL-10 and TNF-α expression was higher than that of the soleus. The IL-10/TNF-α ratio was increased in the skeletal muscle, especially in EDL, but it was found to be decreased in the adipose tissue. These results show that exhaustive exercise presents a different effect depending on the tissue which is analysed: in the muscle, it induces an anti-inflammatory effect, especially in type 2 fibres, while the pro-inflammatory effect prevails in adipose tissue, possibly contributing to increased lipolysis to provide energy for the exercising muscle.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Banzet S, Koulmann N, Simler N, Birot O, Sanchez H, Chapot R, Peinnequin A, Bigard X (2005) Fiber-type specificity of interleukin-6 gene transcription during muscle contraction in rat: association with calcineurin activity. J Physiol 566:839–847. doi:10.1113/jphysiol.2005.089193

    Article  PubMed  CAS  Google Scholar 

  • Banzet S, Koulmann N, Sanchez H, Serrurier B, Peinnequin A, Alonso A, Bigard X (2007) Contraction-induced interleukin-6 transcription in rat slow-type muscle is partly dependent on calcineurin activation. J Cell Physiol 210:596–601. doi:10.1002/jcp.20854

    Article  PubMed  CAS  Google Scholar 

  • Beutler B, Greenwald D, Hulmes JD, Chang M, Pan YC, Mathison J, Ulevitch R, Cerami A (1985) Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature 316(6028):552–554

    Article  PubMed  CAS  Google Scholar 

  • Bury TB, Louis R, Radermecker MF, Pirnay F (1996) Blood mononuclear cells mobilization and cytokines secretion during prolonged exercises. Int J Sports Med 17:156–160. doi:10.1055/s-2007-972825

    Article  PubMed  CAS  Google Scholar 

  • Camus G, Nys M, Poortmans JR, Venneman I, Monfils T, Deby-Dupont G, Juchmès-Ferir A, Deby C, Lamy M, Duchateau J (1998) Endotoxaemia, production of tumour necrosis factor alpha and polymorphonuclear neutrophil activation following strenuous exercise in humans. Eur J Appl Physiol Occup Physiol 79:62–68. doi:10.1007/s004210050474

    Article  PubMed  CAS  Google Scholar 

  • Cawthorn WP, Sethi JK (2008) TNF-alpha and adipocyte biology. FEBS Lett 582:117–131. doi:10.1016/j.febslet.2007.11.051

    Article  PubMed  CAS  Google Scholar 

  • Chan MH, Carey AL, Watt MJ, Febbraio MA (2004) 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. doi:10.1152/ajpregu.00030.2004

    PubMed  CAS  Google Scholar 

  • Dokka S, Shi X, Leonard S, Wang L, Castranova V, Rojanasakul Y (2001) Interleukin-10-mediated inhibition of free radical generation in macrophages. Am J Physiol Lung Cell Mol Physiol 280:L1196–L1202

    PubMed  CAS  Google Scholar 

  • Enevoldsen LH, Stallknecht B, Langfort J, Petersen LN, Holm C, Ploug T, Galbo H (2001) The effect of exercise training on hormone-sensitive lipase in rat intra-abdominal adipose tissue and muscle. J Physiol 536(Pt 3):871–877. doi:10.1111/j.1469-7793.2001.t01-1-00871.x

    Article  PubMed  CAS  Google Scholar 

  • Febbraio MA, Pedersen BK (2002) Muscle-derived interleukin-6: mechanisms for activation and possible biological roles. FASEB J 16:1335–1347. doi:10.1096/fj.01-0876rev

    Article  PubMed  CAS  Google Scholar 

  • Febbraio MA, Ott P, Nielsen HB, Steensberg A, Keller C, Krustrup P, Secher NH, Pedersen BK (2003) Hepatosplanchnic clearance of interleukin-6 in humans during exercise. Am J Physiol Endocrinol Metab 285:E397–E402

    PubMed  CAS  Google Scholar 

  • Fischer CP (2006) Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc Immunol Rev 12:6–33

    PubMed  Google Scholar 

  • Gesta S, Blüher M, Yamamoto Y, Norris AW, Berndt J, Kralisch S, Boucher J, Lewis C, Kahn CR (2006) Evidence for a role of developmental genes in the origin of obesity and body fat distribution. Proc Natl Acad Sci USA 103:6676–6681. doi:10.1073/pnas.0601752103

    Article  PubMed  CAS  Google Scholar 

  • Gomez-Merino D, Drogou D, Guezennec CY, Chennaoui M (2007) Effects of chronic exercise on cytokine production in white adipose tissue and skeletal muscle of rats. Cytokine 40:23–29. doi:10.1016/j.cyto.2007.07.188

    Article  PubMed  CAS  Google Scholar 

  • Helge JW, Stallknecht B, Pedersen BK, Galbo H, Kiens B, Richter EA (2003) The effect of graded exercise on IL-6 release and glucose uptake in human skeletal muscle. J Physiol 546:299–305. doi:10.1113/jphysiol.2002.030437

    Article  PubMed  CAS  Google Scholar 

  • Hirose L, Nosaka K, Newton M, Laveder A, Kano M, Peake J, Suzuki K (2004) Changes in inflammatory mediators following eccentric exercise of the elbow flexors. Exerc Immunol Rev 10:75–90

    PubMed  Google Scholar 

  • Hiscock N, Chan MH, Bisucci T, Darby IA, Febbraio MA (2004) Skeletal myocytes are a source of interleukin-6 mRNA expression and protein release during contraction: evidence of fiber type specificity. FASEB J 18:992–994

    PubMed  CAS  Google Scholar 

  • Ikeda M, Ohira H, Toyama Y, Katagiri T, Sakakibara B (2007) Effect of intestinal microflora on the production of interleukin 10 and prostaglandin E(2) in serum and Kupffer cells from germ free and conventional mice. J Clin Biochem Nutr 41:169–174. doi:10.3164/jcbn.2007023

    Article  PubMed  CAS  Google Scholar 

  • Jonsdottir IH, Schjerling P, Ostrowski K, Asp S, Richter EA, Pedersen BK (2000) Muscle contractions induce interleukin-6 mRNA production in rat skeletal muscles. J Physiol 528:157–163. doi:10.1111/j.1469-7793.2000.00157.x

    Article  PubMed  CAS  Google Scholar 

  • Kaur K, Sharma AK, Dhingra S, Singal PK (2006) Interplay of TNF-alpha and IL-10 in regulating oxidative stress in isolated adult cardiac myocytes. J Mol Cell Cardiol 41:1023–1030. doi:10.1016/j.yjmcc.2006.08.005

    Article  PubMed  CAS  Google Scholar 

  • Kim HJ, Higashimori T, Park SY, Choi H, Dong J, Kim YJ, Noh HL, Cho YR, Cline G, Kim YB, Kim JK (2004) Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo. Diabetes 53:1060–1067. doi:10.2337/diabetes.53.4.1060

    Article  PubMed  CAS  Google Scholar 

  • Lafontan M, Berlan M (2003) Do regional differences in adipocyte biology provide new pathophysiological insights? Trends Pharmacol Sci 24:276–283. doi:10.1016/S0165-6147(03)00132-9

    Article  PubMed  CAS  Google Scholar 

  • Leonidou L, Mouzaki A, Michalaki M, DeLastic AL, Kyriazopoulou V, Bassaris HP, Gogos CA (2007) Cytokine production and hospital mortality in patients with sepsis induced stress hyperglycemia. J Infect 55:340–346. doi:10.1016/j.jinf.2007.05.177

    Article  PubMed  Google Scholar 

  • Lira F, Rosa J, Yamashita A, Koyama C, Batista M Jr, Seelaender M (2009) Endurance training induces depot-specific changes in IL-10/TNF-alpha ratio in rat. Cytokine 45:80–85. doi:10.1016/j.cyto.2008.10.018

    Article  PubMed  CAS  Google Scholar 

  • Mastorakos G, Pavlatou M (2005) Exercise as a stress model and the interplay between the hypothalamus–pituitary–adrenal and the hypothalamus–pituitary–thyroid axes. Horm Metab Res 37:577–584. doi:10.1055/s-2005-870426

    Article  PubMed  CAS  Google Scholar 

  • Mathur N, Pedersen BK (2008) Exercise as a mean to control low-grade systemic inflammation. Mediat Inflamm Epub 2009(Jan)

  • Meador BM, Krzyszton CP, Johnson RW, Huey KA (2008) Effects of IL-10 and age on IL-6, IL-1beta, and TNF-alpha responses in mouse skeletal and cardiac muscle to an acute inflammatory insult. J Appl Physiol 104:991–997. doi:10.1152/japplphysiol.01079.2007

    Article  PubMed  CAS  Google Scholar 

  • Nieman DC, Davis JM, Henson DA, Gross SJ, Dumke CL, Utter AC, Vinci DM, Carson JA, Brown A, McAnulty SR, McAnulty LS, Triplett NT (2005) Muscle cytokine mRNA changes after 2.5 h of cycling: influence of carbohydrate. Med Sci Sports Exerc 37:1283–1290. doi:10.1249/01.mss.0000175054.99588.b1

    Google Scholar 

  • Northoff H, Berg A (1991) Immunologic mediators as parameters of the reaction to strenuous exercise. Int J Sports Med 12:S9–S15. doi:10.1055/s-2007-1024743

    Article  PubMed  Google Scholar 

  • Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen BK (1999) Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. J Physiol 515:287–291. doi:10.1111/j.1469-7793.1999.287ad.x

    Article  PubMed  CAS  Google Scholar 

  • Park PH, Huang H, McMullen MR, Bryan K, Nagy LE (2008) Activation of cyclic-AMP response element binding protein contributes to adiponectin-stimulated interleukin-10 expression in RAW 264.7 macrophages. J Leukoc Biol 83:1258–1266. doi:10.1189/jlb.0907631

    Google Scholar 

  • Pedersen BK (2007) IL-6 signalling in exercise and disease. Biochem Soc Trans 35:1295–1297. doi:10.1042/BST0351295

    Article  PubMed  CAS  Google Scholar 

  • Pedersen BK, Fischer CP (2007) Physiological roles of muscle-derived interleukin-6 in response to exercise. Curr Opin Clin Nutr Metab Care 10(3):265–271. doi:10.1097/MCO.0b013e3280ebb5b3

    Article  PubMed  CAS  Google Scholar 

  • Penkowa M, Keller C, Keller P, Jauffred S, Pedersen BK (2003) Immunohistochemical detection of interleukin-6 in human skeletal muscle fibers following exercise. FASEB J 17:2166–2168

    PubMed  CAS  Google Scholar 

  • Peterson JM, Feeback KD, Baas JH, Pizza FX (2006) Tumor necrosis factor-alpha promotes the accumulation of neutrophils and macrophages in skeletal muscle. J Appl Physiol 101:1394–1399. doi:10.1152/japplphysiol.01453.2005

    Article  PubMed  CAS  Google Scholar 

  • Plomgaard P, Penkowa M, Pedersen BK (2005) Fiber type specific expression of TNF-alpha, IL-6 and IL-18 in human skeletal muscles. Exerc Immunol Rev 11:53–63

    PubMed  Google Scholar 

  • Pond C (1999) Physiological specialisation of adipose tissue. Prog Lipid Res 38:225–248. doi:10.1016/S0163-7827(99)00003-X

    Article  PubMed  CAS  Google Scholar 

  • Raue U, Slivka D, Jemiolo B, Hollon C, Trappe S (2007) Proteolytic gene expression differs at rest and after resistance exercise between young and old women. J Gerontol A Biol Sci Med Sci 62:1407–1412

    PubMed  Google Scholar 

  • Roher N, Samokhvalov V, Díaz M, MacKenzie S, Klip A, Planas JV (2008) The proinflammatory cytokine tumor necrosis factor-alpha increases the amount of glucose transporter-4 at the surface of muscle cells independently of changes in interleukin-6. Endocrinology 149:1880–1889. doi:10.1210/en.2007-1045

    Article  PubMed  CAS  Google Scholar 

  • Ruan H, Lodish HF (2003) Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha. Cytokine Growth Factor Rev 14:447–455. doi:10.1016/S1359-6101(03)00052-2

    Article  PubMed  CAS  Google Scholar 

  • Schottelius AJ, Mayo MW, Sartor RB, Baldwin AS Jr (1999) Interleukin-10 signaling blocks inhibitor of kappaB kinase activity and nuclear factor kappaB DNA binding. J Biol Chem 274:31868–31874. doi:10.1074/jbc.274.45.31868

    Article  PubMed  CAS  Google Scholar 

  • Schulz KH, Gold SM, Witte J, Bartsch K, Lang UE, Hellweg R, Reer R, Braumann KM, Heesen C (2004) Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis. J Neurol Sci 225:11–18. doi:10.1016/j.jns.2004.06.009

    Article  PubMed  CAS  Google Scholar 

  • Sjorgreen B,Nordenskjold T, Holmgren H, Wollestron J (1938) Beitrag zur kentnis des lebenrhythmik. Pflugers Arch Ges Phys 240–247

  • Sprenger H, Jacobs C, Nain M, Gressner AM, Prinz H, Wesemann W, Gemsa D (1992) Enhanced release of cytokines, interleukin-2 receptors, and neopterin after long-distance running. Clin Immunol Immunopathol 63:188–195. doi:10.1016/0090-1229(92)90012-D

    Article  PubMed  CAS  Google Scholar 

  • Starkie RL, Angus DJ, Rolland J, Hargreaves M, Febbraio MA (2000) Effect of prolonged, submaximal exercise and carbohydrate ingestion on monocyte intracellular cytokine production in humans. J Physiol 528:647–655. doi:10.1111/j.1469-7793.2000.t01-1-00647.x

    Article  PubMed  CAS  Google Scholar 

  • Steensberg A, Fischer CP, Keller C, Moller K, Pedersen BK (2003) IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab 285:E433–E437

    PubMed  CAS  Google Scholar 

  • Suganami T, Tanimoto-Koyama K, Nishida J, Itoh M, Yuan X, Mizuarai S, Kotani H, Yamaoka S, Miyake K, Aoe S, Kamei Y, Ogawa Y (2007) Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Thromb Vasc Biol 27:84–91. doi:10.1161/01.ATV.0000251608.09329.9a

    Article  PubMed  CAS  Google Scholar 

  • Suzuki K, Yamada M, Kurakake S, Okamura N, Yamaya K, Liu Q, Kudoh S, Kowatari K, Nakaji S, Sugawara K (2000) Circulating cytokines and hormones with immunosuppressive but neutrophil-priming potentials rise after endurance exercise in humans. Eur J Appl Physiol 81:281–287. doi:10.1007/s004210050044

    Article  PubMed  CAS  Google Scholar 

  • Suzuki K, Nakaji S, Yamada M, Liu Q, Kurakake S, Okamura N, Kumae T, Umeda T, Sugawara K (2003) Impact of a competitive marathon race on systemic cytokine and neutrophil responses. Med Sci Sports Exerc 35:348–355. doi:10.1249/01.MSS.0000048861.57899.04

    Article  PubMed  CAS  Google Scholar 

  • Suzuki K, Peake J, Nosaka K, Okutsu M, Abbiss CR, Surriano R, Bishop D, Quod MJ, Lee H, Martin DT, Laursen PB (2006) Changes in markers of muscle damage, inflammation and HSP70 after an Ironman triathlon race. Eur J Appl Physiol 98:525–534. doi:10.1007/s00421-006-0296-4

    Article  PubMed  CAS  Google Scholar 

  • Torti FM, Dieckmann B, Beutler B, Cerami A, Ringold GM (1985) A macrophage factor inhibits adipocyte gene expression: an in vitro model of cachexia. Science 229(4716):867–869

    Article  PubMed  CAS  Google Scholar 

  • Trujillo ME, Sullivan S, Harten I, Schneider SH, Greenberg AS, Fried SK (2004) Interleukin-6 regulates human adipose tissue lipid metabolism and leptin production in vitro. J Clin Endocrinol Metab 89:5577–5582. doi:10.1210/jc.2004-0603

    Article  PubMed  CAS  Google Scholar 

  • Vohl MC, Sladek R, Robitaille J, Gurd S, Marceau P, Richard D, Hudson TJ, Tchernof A (2004) A survey of genes differentially expressed in subcutaneous and visceral adipose tissue in men. Obes Res 12:1217–1222. doi:10.1038/oby.2004.153

    Article  PubMed  CAS  Google Scholar 

  • Zaldivar F, Wang-Rodriguez J, Nemet D, Schwindt C, Galassetti P, Mills PJ, Wilson LD, Cooper DM (2006) Constitutive pro- and anti-inflammatory cytokine and growth factor response to exercise in leukocytes. J Appl Physiol 100:1124–1133. doi:10.1152/japplphysiol.00562.2005

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Emilia Ribeiro for her technical assistance. This work was supported by Grant No. 04/11588-0 and 05/01445-0 from the FAPESP.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cláudia M. Oller do Nascimento.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rosa Neto, J.C., Lira, F.S., Oyama, L.M. et al. Exhaustive exercise causes an anti-inflammatory effect in skeletal muscle and a pro-inflammatory effect in adipose tissue in rats. Eur J Appl Physiol 106, 697–704 (2009). https://doi.org/10.1007/s00421-009-1070-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-009-1070-1

Keywords

Navigation