Journal of Orthopedic Research and Therapy (ISSN: 2575-8241)

Article / research article

"Physical Exercise and the Inflammatory Effect on Skeletal Muscle Due To Interleukin-6"

Haron Silva Dorta*

Department of Physiotherapist, Rehabilitation specialist, Master in Sciences, Universidade Federal de São Paulo, Escola Paulista de Medicina, UNIFESP-EPM, Brazil

*Corresponding author:  Haron Silva Dorta, Department of Physiotherapist, Rehabilitation specialist, Master in Sciences, Street Pedro de Toledo, 669, 11ºandar, L11E; Vila Clementino - São Paulo-SP , Brazil. Tel: +04039-032; E-mail:

Received Date: 21 September, 2016; Accepted Date: 24 October, 2016; Published Date: 18 February, 2017

Interleukin-6 (IL-6) is a cytokine acting both the innate and the adaptive immune response. Their relationship is in pro inflammatory, presenting in great evidence for the practice of physical exercise but its activities extend to other organ. Depending on the type of exercise and IL-6 increases the frequency quantity in muscle tissue and into the bloodstream. Its performance is in large muscular system and your understanding is of great importance for the treatment of conditions in other systems.

Keywords: Physical exercise; Skeletal muscle; Interleukin-6


Physical exercise is associated with numerous benefits, but its practice is a causative stress factor for muscle tissue [1]. The practice and the physiological responses found during the exercises are related to your period of practice, intensity, time and frequency [2].All these variants of physical training is correlated with muscle response directly proportional to the type of muscle fiber [3]. During the practice of physical activity can induce an inflammatory response, by increases in serum levels of IL-1, TNF-α and IL-6 cytokine responsive, followed by release of anti-inflammatory cytokines such as IL-10, and IL-1ra, sTNF-R2 are inhibitors of pro-inflammatory cytokines [4]. Interleukin-6 (IL-6) is a cytokine acting both the innate and the adaptive immune response. It is synthesized by monocytes, endothelial cells, fibroblasts and other cells in response to microorganisms and also to stimulation by other cytokines, particularly interleukin-1 (IL-1) and tumor necrosis factor (TNF-α) [5].

Physical Exercise

Exercise is defined as any body movement, held with the participation of skeletal muscle involving a higher energy expenditure when compared to resting levels, being carried out through repetitive body movements, structured and planned, resulting in an improvement of one or more components of physical fitness [6].

When it comes to exercise their benefit level is huge, thanks to physical exercise have the control of body weight, modulation of blood glucose levels and reduce other metabolic factors and the development of cardiovascular disease [7]. Improved immune system [8], improvement of the cardiopulmonary system [9], the operation of increasing the renal system [10], increased levels of neuronal connections [11], increasing muscle mass [12], the release of endorphins [13], and decreased levels of body fat [14]. But there are some variables that influence the way in which the exercise is applied as frequency, mode, duration, intensity, and factors such as diet, physical conditioning that can also modify the effect of exercise [15].

Physical Exercises Types

There are two types of exercises, acute and chronic, the responses of muscle metabolism to acute or chronic physical exercise demonstrate high level of dependence of methodological schemes used in their research. The various existing studies show wide variation in relation to the methodological approach, making comparisons problematic some possible [16]. Although the exercise be broadly classified as a stressful stimulus looks more appropriate to divide the response to exercise of two components: acute and chronic response [17].

Acute Physical Exercise          

The exercise term acute refers to the physiological responses that occur when the exercise is being developed [18]. The performance of acute exercise has shown effects on some physiological parameters such as blood lipid concentrations, lipoproteins, cholesterol, blood pressure, glucose metabolism, immune system, and many other variables [19,20]. The acute response is transient reaction to stress while the chronic stimulation generates chronic adaptation response to exercise, which enables the body to tolerate more adequately stress [21,22].

Chronic Physical Exercises

Chronic exercise term refers to the chronic adaptation response to exercise, which enables the body to tolerate more adequately subjected to stress during their practice [23,24]. The physical exercises practiced regularly or chronic lead to important physiological and morphological adaptations to maintain the homeostasis of the organism and these adjustments are important for the control of many diseases, particularly cardiovascular and endocrine-metabolic nature [25,26].

Physical Training Form

It is known that physical activity is a known form of stress and chronic exposure to it, called physical training [27], is able to trigger adaptations in response to higher production of these free radicals. There are two different forms of training, training with aerobic [28] exercise and anaerobic [29].

Anaerobic Exercises

Anaerobic exercise is defined as high-intensity, short duration exercise (up to 3 minutes), energy is mainly obtained from the first system, without participation of oxygen [30,31]. The resistance or anaerobic exercises seem to prevent more sharply the loss of muscle mass, and increase glucose utilization [32].

Aerobic Exercises

Aerobic exercises are those that have long duration and the intensity of which can be low, moderate or high, keeping however the measured pace, causing improvement in oxygen transport to the cellular level, developing aerobic endurance, and is also called cyclic exercises [33,34]. The regular practice of aerobic exercise provides, both at rest and during exercise, lower heart rate and increased stroke volume. The regular practice of progressive exercises (chronic), determines the maximum cardiac output increase, slight increase in the filling pressures of the heart during exercise, but normal at home, and dilatation and hypertrophy of the heart [35,36].

Skeletal Muscle Fibers

Skeletal muscles were initially classified as slow and fast, in accordance with its prevailing conditions (aerobic or anaerobic) [37,38]. Since the muscle fibers are classified by type I fibers (slow), type II fibers (fast) and Type IIb fibers (intermediate) [39]. Type I fibers or slow fibers, also called tonic, have reddish color due to the presence of oxygen bound to the protein myoglobin, and have a large number of mitochondria, and most of them are located near the peripheral region fiber [40]. This type of fiber is more resistant to fatigue, mainly in exercises that require longer time (aerobic), and its power source is from oxidative metabolism to generate ATP [41,42]. Type II fibers, or fast-twitch fibers, also called phasic or dynamic, have white color with a small amount of myoglobin, being replaced by enzymes in the glycolytic type [43]. Have a reduced number of mitochondria, are poorly vascularized and use glucose for their energy with minimal or no use of oxygen (anaerobic), being able to intend intensely, with great strength and power, because its long fibers allow for contraction and relaxation in a very rapid sequence with a more explosive action, being more efficient for high-speed and power peaks. But fatigue very quickly, only resisting short term exercise (anaerobic) [44,45]. The fibers of the type IIb, classified as intermediate, possess features of two other types, such as the fact that metabolize glucose and oxygen to obtain energy. We may have changes in their predominance according to the stimulus to which it is subjected during exercise [46,47].


Interleukin-6 (IL-6) is a cytokine acting both the innate and the adaptive immune response. It is synthesized by monocytes, endothelial cells, fibroblasts and other cells in response to microorganisms and also to stimulation by other cytokines, particularly interleukin-1 (IL-1) and tumor necrosis factor (TNF-α) [48]. The IL-6 is an important inflammatory marker. It is a cytokine involved in a number of immunological activities, in particular the synthesis of acute phase substances by the liver and is involved in the metabolic regulation of the PCR itself. Like its receptor (gp130), is widely expressed during the inflammatory reaction, producing undesirable effects on various organs [48,49]. The In skeletal muscle, the elevation of pro inflammatory cytokines such as IL-6, is associated with the incidence of damage to the muscle tissue induced high-intensity activities or actions eccentric [50]. However, subsequent studies established that IL-6 may increase even in the absence of injury [50,51]. The IL-6 plasma during exercise increases with the intensity and duration of activity in IL-6 can be regarded as a "exercise factor"; this cytokine, which is produced and released in skeletal muscle in response to exercise, exerts its effects in other organs of the body [50,51]. In this sense, as adipokines term was established for cytokines and other peptides that are produced and secreted by adipocytes, the term myokines, can be used to cytokines and other peptides that are produced and released by muscle fibers [50,52].

The Cytokines can be classified according to their function, pro inflammatory or anti-inflammatory. Pro-inflammatory cytokines induce increased inflammatory process, such as for example, interleukin-1β (IL-1β), interleukin-6 (IL-6), Interleukin-8 (IL-8), tumor necrosis factor (TNF-α), interferon (IFN), interleukin-2 (IL-2) and chemokines. The anti-inflammatory cytokines are characterized by decreased inflammation by regulating inflammation by restriction pro inflammatory cytokines, among which are: interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-13 (IL-13), as well as receptor antagonist of IL-1 (IL-1ra) [52,53].

Interleukin-6 Is The Physical Exercise

Physical exercise can be regarded as a prototype of physical stress. Many clinical physical stressors (eg surgery, trauma, burn, sepsis) induce a pattern of hormonal and immunological responses to have Similarities of exercise [54]. During the practice of physical exercise suffer functional changes in the immune system, and the response generated depends on the volume and intensity of training [55]. Physical activity can induce an inflammatory response, by increases in serum levels of IL-1, TNF-α and IL-6 cytokine responsive, followed by release of anti-inflammatory cytokines such as IL-10 and IL-1ra , sTNF-R2 are inhibitors of pro-inflammatory cytokines. So the type, duration and intensity of exercise are major factors for the profile of response of cytokines after exercise [56,57]. In a frame where the IL-6 increases exponentially in response to exercise and reduces post exercise period (Figure 1).

Where is occurring IL-6 plasma increases it is related to the duration of the exercise, since IL-6 mRNA is regulated by muscle contraction, so the rate of transcription of this gene is enhanced by exercise, however, some factors stimulate IL-6 release including: changes in calcium homeostasis, low levels of muscle glycogen and increases the formation of reactive oxygen species [57-59]. With the carbohydrate supplementation inhibits the increase of IL-6 induced by exercise, because it affects the expression of mRNA for IL-6. The IL-6 synthesized in response to exercise can act locally in the muscle or may be released into circulation, being able to induce systemic effects by controlling energy metabolism [54,55,60]. This mechanism is associated with stimulation of protein kinase route activated by AMP (AMPK), which is increased by IL-6, suggesting that activation of AMPK in muscle tissue depends on IL-6, stimulates AMPK activity several mechanisms, that increase the generation of ATP, including fatty acid oxidation and glucose transport in skeletal muscle [61,62]. The exercise-induced Increase of plasma IL-6 is not linear over time; During exercise repeated measurements show an accelerating Increase of the IL-6 in plasma in an almost exponential mannered, Furthermore, the peak IL-6 level is Reached at the end of the exercise or shortly thereafter, Followed by the rapid decrease towards pre-exercise levels [54,60].

The IL-6 level in blood Has Been shown to be Significantly enhanced 30 min after the start of running, peaking at the end of 2.5 h of running.14 In other studies, where IL-6 has not Been measured During the running but at several team points after, maximal-IL-6 levels Have Been found immediately after the exercise Followed by the rapid decline (half-life of 1-2 h). Thus, Following the marathon run, maximal IL-6 levels (100-fold Increase) Have Been measured immediately after the 3-3.5 h race [54,60].


In our review we conclude that the training status and performance on plasma IL-6 concentration changes are more inconclusive During exercise, your peak predominated is pos training and studies should be conducted to verify the skeletal muscle is an endocrine organ in response to contractions produces and releases 'myokines', Which subsequently can modulate the metabolic and immunological response to exercise in several tissues.

Figure 1: Demonstrates a few steps from the exercise and the formation of IL-6 in skeletal muscle and hepatic system.

1.       Egan B and Zierath JR (2013) Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab 17: 162-184. 
2.       Williams CA, Benden C, Stevens D, Radtke T (2010) Exercise training in children and  adolescents with cystic fibrosis: theory into practice. Int J Pediatr 2010.
3.       Widrick JJ, Stelzer JE, Shoepe TC, Garner DP (2002) Functional properties of human muscle fibers after short-term resistance exercise training. Am J PhysiolRegulIntegr Comp Physiol 283: R408-416.
4.       Pinto A, Di Raimondo D, Tuttolomondo A, Buttà C, Milio G, et al. (2012) Effects ofphysical exercise on inflammatory markers of atherosclerosis. Curr Pharm Des 18: 4326-4349.
5.       Garlanda C, Dinarello CA, Mantovani A (2013) The interleukin-1 family: back to the future. Immunity 39: 1003-1018. 
6.       Caspersen CJ, Powell KE, Christenson GM (1985) Physical activity, exercise and physical fitness: definitions and distinctions for health-related research. Public Health Rep 100: 126-131.
7.       Bherer L, Erickson KI, Liu-Ambrose T (2013) A review of the effects of physical activity and exercise on cognitive and brain functions in older adults. J Aging Res 2013: 657508. 
8.       Passos GS, Poyares D, Santana MG, Teixeira AA, Lira FS, et al. (2014) Exercise improves immune function, antidepressive response, and sleep quality in patients with chronic primary insomnia. Biomed Res Int 2014: 498961. 
9.       MacKay-Lyons MJ and Howlett J (2005) Exercise capacity and cardiovascular adaptations to aerobic training early after stroke. Top Stroke Rehabil 12: 31-44. 
10.    Shi ZM, Wen HP, Liu FR, Yao CX (2014) The effects of tai chi on the renal and cardiac functions of patients with chronic kidney and cardiovascular diseases. J  Phys Ther Sci 26: 1733-1736.
11.    Kirk-Sanchez NJ and McGough EL (2014) Physical exercise and cognitive performance in the elderly: current perspectives. ClinInterv Aging 9: 51-62. 
12.    Witard OC, Jackman SR, Breen L, Smith K, Selby A, et al. (2014) Myofibrillar muscle protein synthesis rates subsequent to a meal in response to increasing doses of whey protein at rest and after resistance exercise. Am J ClinNutr 99: 86-95.
13.    Daenen L, Varkey E, Kellmann M, Nijs J (2015) Exercise, not to exercise, or how to exercise in patients with chronic pain? Applying science to practice. Clin J Pain 31: 108-114. 
14.    Swisher AK, Abraham J, Bonner D, Gilleland D, Hobbs G, et al. (2015) Exercise and dietary advice intervention for survivors of triple-negative breast cancer: effects on body fat, physical function, quality of life, and adipokine profile. Support Care Cancer 23: 2995-3003.
15.    WHITE RD and SHERMAN C (1999) Exercise in Diabetes Management. The physician and sport medicine 4: 7. 
16.    Ward CW, Spangenburg EE, Diss LM, Williams JH (1998) Effects of varied fatigue protocols on sarcoplasmic reticulum calcium uptake and release rates. Am J Physiol 275: R99-R104. 
17.    Nieman DC (1998) Influence of carbohydrate on the immune response to intensive, prolonged exercise. ExercImmunol Rev 4: 64-76. 
18.    Nóbrega ACL (2005) The subacutes effects of exercise: concept, characteristics, and clinical implications. Exerc. Sport Sci. Rev 33: 84-87. 
19.    Thompson PD, Crouse SF, Goodpaster B, Kelley D, Moyna N, et al. (2001) The acute versus the chronic response to exercise. Med Sci Sports Exerc 33: S438-445.
20.    Rowbottom, DAVID G and KATHERINE J. Green (2000) "Acute exercise effects on the immune system." Medicine and science in sports and exercise 32: S396-405. 
21.    Norheim F, Langleite TM, Hjorth M, Holen T, Kielland A, et al. (2014) The effects of acute and chronic exercise  on PGC-1α, irisin and browning of subcutaneous adipose tissue in humans. FEBS J 281: 739-749. 
22.    Bruneau ML Jr, Johnson BT, Huedo-Medina TB, Larson KA, Ash GI, et al. (2015) The blood pressure response to acute and chronic aerobic exercise: A meta-analysis of candidate gene association studies. J Sci Med Sport 2015: S1440-2440. 
23.    Cannon JG, Meydani SN, Fielding RA (1991) Acute phase response in exercise. Part II: associations between vitamin E, cytokines, and muscle proteolysis. Am J Physiol 260: R1235-1240.
24.    Hawley and John A., Michael J Joyner, Juleen R Zierath (2014) "Integrative biology of exercise."159: 738-749. 
25.    Cartee GD and Farrar RP (1988) Exercise training induces glycogen sparing during exercise by old rat. J ApplPhysiol 64: 259-265.
26.    Ling Charlotte and Tina Rönn (2014) "Epigenetic adaptation to regular exercise in humans." Drug discovery today 19: 1015-1018. 
27.    King AC, Stokols D, Talen E, Brassington GS, Killingsworth R (2002) Theoretical approaches to the promotion of physical activity: forging a transdisciplinary paradigm. Am J Prev Med 23: 15-25. 
28.    Wilson JM, Marin PJ, Rhea MR, Wilson SM, Loenneke JP, et al. (2012) Concurrent training: a meta-analysis examining interference of aerobic and resistance exercises. J Strength Cond Res 26: 2293-2307.
29.    Gómez-Cabello A, Ara I, González-Agüero A, Casajús JA (2012) Vicente-Rodríguez G.Effects of training on bone mass in older adults: a systematic review. Sports Med 42: 301-325. 
30.    Calbet JA, Rådegran G, Boushel R, Saltin B (2009) On the mechanisms that limit oxygen uptake during exercise in acute and chronic hypoxia: role of muscle mass. J Physiol 587: 477-490.
31.    Hollmann W (1985) Historical remarks on the development of the aerobic-anaerobic threshold up to 1966. Int J Sports Med 6: 109-116.
32.    Zelber-Sagi S, Buch A, Yeshua H, Vaisman N, Webb M, et al. (2014) Effect of resistance training on non-alcoholic fatty-liver disease a randomized-clinical trial. World J Gastroenterol 20: 4382-4392.  
33.    Roghani T, Torkaman G, Movasseghe S, Hedayati M, Goosheh B, et al. (2013) Effects of short-term aerobic exercise with and without external loading on bone metabolism and balance in postmenopausal women with osteoporosis. Rheumatol Int 33: 291-298.
34.    Silva and Luciano Flausino da (2012) "A importãncia do exercício físico na vida do idoso." 2012. 
35.    Mang CS, Snow NJ, Campbell KL, Ross CJ, Boyd LA (1985) A single bout of high-intensity aerobic exercise facilitates response to paired associative stimulation and promotes sequence-specific implicit motor learning. J ApplPhysiol 117: 1325-1336.
36.    Horner K, Kuk JL, Barinas-Mitchell E, Drant S, DeGroff C, et al. (2015) Effect of Aerobic Versus Resistance Exercise on Pulse Wave Velocity, Intima Media Thickness and Left Ventricular Mass in Obese Adolescents. PediatrExerc Sci 7: 494-502. 
37.    MORRIS C (1986) Human muscle fiber type grouping and collateral re-innervation. J.Neurol. Neurosurg. Psychiatr 32: 440-444.
38.    Allen DG, Lamb GD, Westerblad H (2008) Skeletal muscle fatigue: cellular mechanisms. Physiol Rev 88: 287-332. 
39.    Staron RS, Kraemer WJ, Hikida RS, Reed DW, Murray JD, et al. (1998) Comparison of soleus muscles from rats exposed to microgravity for 10 versus 14 days. Histochem Cell Biol 110: 73-80.
40.    Spangenburg EE and Booth FW (2003) Molecular regulation of individual skeletal muscle fibre types. ActaPhysiol Scand 178: 413-424. 
41.    Tam BT, Pei XM, Yu AP, Sin TK, Leung KK, et al. (2015) Autophagic adaptation is associated with exercise-induced fibre-type shifting in skeletal muscle. ActaPhysiol 214: 221-236.
42.    Hvid LG, Gejl K, Bech RD, Nygaard T, Jensen K, et al. (2013) Transient impairments in single muscle fibre contractile function after prolonged cycling in elite endurance athletes. ActaPhysiol (Oxf) 208: 265-273. 
43.    Curry JW, Hohl R, Noakes TD, Kohn TA (2012) High oxidative capacity and type IIxfibre content in springbok and fallow deer skeletal muscle suggest fast sprinters with a resistance to fatigue. J Exp Biol. 215: 3997-4005. 
44.    Yoshihara H, Wakamatsu J, Kawabata F, Mori S, Haruno A, et al. (2006) Beef extract supplementation increases leg muscle mass and modifies skeletal muscle fiber types in rats. J NutrSciVitaminol (Tokyo) 52:183-193. 
45.    Gillies EM, Putman CT, Bell GJ (2006) The effect of varying the time of concentric and eccentric muscle actions during resistance training on skeletal muscle adaptations in women. Eur J Appl Physiol 97: 443-53. 
46.    D'Antona G, Lanfranconi F, Pellegrino MA, Brocca L, Adami R, et al. (2006) Skeletal muscle hypertrophy and structure and function of skeletal muscle fibres in male body builders. J Physiol 570: 611-627. 
47.    Kim JH and Thompson LV (2014) Non-weight bearing-induced muscle weakness: the role of myosin quantity and quality in MHC type II fibers. Am J Physiol Cell Physiol 307: C190-194.
48.    Gomes, Marco Antônio Mota, Nilton Cavalcanti Macêdo Neto, Irving Gabriel Araújo Bispo (2009) "Interleucina-6, moléculas de adesão intercelular-1 e microalbuminúria na avaliação da lesão endotelial: revisão de literatura." 22: 398-403.
49.    Tonet AC, Karnikowski M, Moraes CF, Gomes L, Karnikowski MGO, et al.  (2008) Association between the -174 G/C promoter polymorphism of the interleukin- 6 gene and cardiovascular disease risk factors in Brazilian older women. Braz J Med Biol Res 41: 47-53.
50.    Prestes, Jonat, et al. (2006) "Papel da Interleucina-6 como um sinalizador em diferentes tecidos durante o exercício físico." Fitness & performance journal 6: 348-353.
51.    Pedersen BK, Steensberg A, Fischer C, Keller C, Keller P, et al. (2004) The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor? Proc Nutr Soc 63: 263-267.
52.    Pedersen BK and Febbraio M (2005) Muscle-derived interleukin-6—A possible link between skeletal muscle, adipose tissue, liver, and brain. Brain Behav Immunity 19: 371-376.
53.    Carvalho, Wilson Andrade, Lino Lemônica (1998) "Mecanismos celulares e moleculares da dor inflamatória. Modulação periférica e avanços terapêuticos." Revista Brasileira de Anestesiologia 48: 137-158.
54.    Pedersen Bente Klarlund (2000) Exercise and cytokines. Immunology and cell biology 78: 532-535. 
55.    Pedersen BK, Hoffman-Goetz L (2000) Exercise and the immune system: regulation,integration, and adaptation.Physiol Rev 80: 1055-1081.
56.    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.
57.    Oberholzer A, Oberholzer C, Moldawer LL (2002) Interleukin-10: A complex role in the pathogenesis of sepsis syndromes and its potential as an anti-inflammatory drug. Crit Care Med 30: S58-S63.
58.    Scott JP, Sale C, Greeves JP, Casey A, Dutton J, et al. (2013) Cytokine response to acute running in recreationally-active and endurance-trained men. Eur J Appl Physiol 113: 1871-1882.
59.    Brandt C and Pedersen BK (2010) The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases. J Biomed Biotechnol 2010: 520258.
60.    Pedersen BK and Fischer CP (2007) Physiological roles of muscle-derived interleukin-6 in response to exercise. CurrOpinClinNutrMetab Care 10: 265-271.
61.    O'Neill LA and Hardie DG (2013) Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 493: 346-355.
62.    Hardie DG and Sakamoto K (2006) AMPK: a key sensor of fuel and energy status in skeletal muscle. Physiology (Bethesda) 21: 48-60.


Citation: Dorta HS (2016) Physical Exercise and the Inflammatory Effect on Skeletal Muscle Due To Interleukin-6. J Orthop Res Ther 2017: 114. DOI: 10.29011/2575-8241.000114

free instagram followers instagram takipçi hilesi