Download PDF
Int J Sports Med 2000; 21(Supplement 1): 4-9
DOI: 10.1055/s-2000-1444
Georg Thieme Verlag Stuttgart · New York

Cytokines in Aging and Exercise

B. K. Pedersen,  H. Bruunsgaard,  K. Ostrowski,  K. Krabbe,  H. Hansen,  K. Krzywkowski,  A. Toft,  S. R. Søndergaard,  E. W. Petersen,  T. Ibfelt,  P. Schjerling
  • The Copenhagen Muscle Research Centre, Department of Infectious Diseases, University of Copenhagen, Denmark
Further Information

Publication History

Publication Date:
31 December 2000 (online)

Also available at
    Permissions and Reprints

Aging is associated with increased inflammatory activity. Increased plasma levels of tumour necrosis factor (TNF)-α were found in centenarians aged 100 years and in individuals aged 80 - 81 years when compared to a young control group. Plasma levels of TNF-α were linearly correlated to plasma levels of interleukin (IL)-6, TNF-receptors and C-reactive protein. High levels of TNF-α were directly related to dementia and to a low blood pressure ankle-arm index, indicating generalized atherosclerosis. In hospitalized patients with Streptococcus pneumonia infection, aging was associated with prolonged inflammatory activity. Similar results were found using an in vivo endotoxin challenge model in old versus young humans. Strenuous exercise induces increased levels in a number of proinflammatory and anti-inflammatory cytokines, naturally occurring cytokine inhibitors and chemokines. Thus, increased plasma levels of TNF-α, IL-1, IL-6, IL-1 receptor antagonist (IL-lra), TNF-receptors (TNF-R), IL-10, IL-8 and macrophage inflammatory protein (MIP)-1 are found after strenuous exercise. The cytokine response to strenuous exercise has similarities to the cytokine response to trauma and sepsis. Therefore, in future studies, exercise is suggested as an ethically applicable model to use in studies on mechanisms underlying the age-associated altered cytokine response.

References

  • 1 Bagby G J, Crouch L D, Shepherd R E. Exercise and cytokines: Spontaneous and elicited responses. In: Hoffman-Goetz L (ed) Exercise and Immune Function. New York; CRC Press 1996: 55
    Google Scholar
  • 2 Bosenberg A T, Brock Utne J G, Gaffin S L, Wells M T, Blake G T. Strenuous exercise causes systemic endotoxemia.  J Appl Physiol. 1988;  65 106-108
    PubMedGoogle Scholar
  • 3 Brock Utne J G, Gaffin S L, Wells M T, Gathiram P, Sohar E, James M F, Morrell D F, Norman R J. Endotoxemia in exhausted runners after a long-distance race.  S Afr Med J. 1988;  73 533-536
    PubMedGoogle Scholar
  • 4 Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen A N, Skinhj P, Pedersen B K. A high plasma concentration of TNF-α is associated with dementia in centenarians.  J Gerontology. 1999;  54 (7) 357-364
    PubMedGoogle Scholar
  • 5 Bruunsgaard H, Galbo H, Halkjaer-Kristensen J, Johansen T L, MacLean D A, Pedersen B K. Exercise-induced increase in interleukin-6 is related to muscle damage.  J Physiol Lond. 1997;  499 833-841
    PubMedGoogle Scholar
  • 6 Bruunsgaard H, Skinhoj P, Qvist J, Pedersen B K. Elderly human show prolonged in vivo inflammatory activity during pneumococcal infections.  J Inf Dis. 1999;  180 (2) 551-554
    PubMedGoogle Scholar
  • 7 Cannon J G, Evans W J, Hughes V A, Meredith C N, Dinarello C A. Physiological mechanisms contributing to increased interleukin-1 secretion.  J Appl Physiol. 1986;  61 1869-1874
    PubMedGoogle Scholar
  • 8 Cannon J G, Kluger M J. Endogenous pyrogen activity in humans plasma after exercise.  Science. 1983;  220 617-619
    PubMedGoogle Scholar
  • 9 Castell L M, Poortmans J R, Leclercq R, Brasseur M, Duchateau J, Newsholme E A. Some aspects of the acute phase response after a marathon race, and the effects of glutamine supplementation.  Eur J Appl Physiol. 1997;  75 47-53
    PubMedGoogle Scholar
  • 10 Catania A, Airagi L, Motta P, Manfredi M G, Annoni G, Pettenati C, Brambilla F, Lipton J M. Cytokine antagonists in aged subjets and their relation with cellular immunity.  J Gerontol A Biol Sci Med Sci. 1997;  52 B93-B97
    PubMedGoogle Scholar
  • 11 Croisier J L, Camus G, Venneman I, Deby-Dupont G, Juchmes-Ferir A, Lamy M, Crielaard J M, Deby C, Duchateau J. Effects of training on execise-induced muscle damage and interleukin 6 production.  Muscle Nerve. 1999;  22 208-212
    PubMedGoogle Scholar
  • 12 DeRijk R H, Boelen A, Tilders F J, Berkenbosch F. Induction of plasma interleukin-6 by circulating adrenaline in the rat.  Psychoneuroendocrinology. 1994;  19 155-163
    CrossrefPubMedGoogle Scholar
  • 13 Dinarello C A. Role of interleukin-1 in infectious diseases.  Immunol Rev. 1992;  127 119-146
    PubMedGoogle Scholar
  • 14 Drenth J P, van Uum S H, van Deuren M, Pesman G J, van der ven Jongekrug J, van der Meer J W. Endurance run increases circulating IL-6 and IL-1ra but downregulates ex vivo TNF-α and IL-1β production.  J Appl Physiol. 1995;  79 1497-1503
    PubMedGoogle Scholar
  • 15 Ershler W B, Sun W H, Binkley N, Gravenstein S, Volk M J, Kamoske G, Klopp R G, Roecker E B, Daynes R A, Weindruch R. Interleukin-6 and aging: blood levels and mononuclear cell production increase with advancing age and in vitro production in modifiable by dietary restriction.  Lymphokine Cytokine Res. 1993;  12 225-230
    PubMedGoogle Scholar
  • 16 Evans W J, Meredith C N, Cannon J G, Dinarello C A, Frontera W R, Hughes V A, Jones B H, Knuttgen H G. Metabolic changes following eccentric exercise in trained and untrained men.  J Appl Physiol. 1986;  61 1864-1868
    PubMedGoogle Scholar
  • 17 Hellsten Y, Frandsen U, Orthenblad N, Sjodin N, Richter E A. Xanthine oxidase in human skeletal muscle following eccentric exercise: a role of inflammation.  J Physiol (London). 1997;  498 239-248
    PubMedGoogle Scholar
  • 18 Kania D M, Binkley N, Checovich M, Havighurst T, Schilling M, Ershler W B. Elevated plasma levels of interleukin-6 in postmenopausal women do not correlate with bone density.  J Am Geriatr Soc. 1995;  43 236-239
    PubMedGoogle Scholar
  • 19 Klausen T, Richalet J P, Olsen N V, Pedersen B K. Hypoxemia increases serum interleukin-6 in humans.  Eur J Appl Physiol. 1997;  76 480-482
    CrossrefPubMedGoogle Scholar
  • 20 Martin C, Boisson C, Haccoun M, Thomacot L, Mege J L. Patterns of cytokine evolution (tumor necrosis factor-α and interleukin-6) after septic shock, and severe trauma.  Crit Care Med. 1997;  25 1813-1819
    PubMedGoogle Scholar
  • 21 Moore G E, Holbein M E, Knochel J P. Exercise-associated collapse in cyclists is unrelated to endotoxemia.  Med Sci Sports Exerc. 1995;  27 1238-1242
    PubMedGoogle Scholar
  • 22 Nehlsen Cannarella S L, Fagoaga O R, Nieman D C, Henson D A, Butterworth D E, Schmitt R L, Bailey E M, Warren B J, Utter A, Davis J M. Carbohydrate and the cytokine response to 2.5 h of running.  J Appl Physiol. 1997;  82 1662-1667
    PubMedGoogle Scholar
  • 23 Nielsen S V, Henrichsen J. Incidence of invasive pneumococcal disease and distribution of capsular types of pneumococci in Denmark.  Epidemiology and Infection. 1996;  117 411-416
    PubMedGoogle Scholar
  • 24 Northoff H, Berg A. Immunologic mediators as parameters of the reaction to strenuous exercise.  Int J Sports Med. 1991;  12 S9-S15
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Ostrowski K, Hermann C, Bangash A, Schjerling P, Nielsen J N, Pedersen B K. A trauma-like elevation in plasma cytokines in humans in response to treadmill running.  J Physiol (London). 1998;  508 949-953
    CrossrefPubMedGoogle Scholar
  • 26 Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen B K. The cytokine balance and strenuous exercise: TNF-α, IL-2β, IL-6, IL-1ra, sTNF-r1, sTNF-r2, and IL-10.  J Physiol (London). 1999;  515 287-291
    CrossrefPubMedGoogle Scholar
  • 27 Ostrowski K, Rohde T, Zacho M, Asp S, Pedersen B K. Evidence that IL-6 is produced in skeletal muscle during intense long-term muscle activity.  J Physiol (London). 1998;  508 949-953
    CrossrefPubMedGoogle Scholar
  • 28 Pedersen B K, Ostrowski K, Rohde T, Bruunsgaard H. The cytokine response to strenuous exercise.  Can J Physiol Pharmacol. 1998;  76 505-511
    CrossrefPubMedGoogle Scholar
  • 29 Richards C, Gauldie J. Role of cytokines in acute-phase response. In: Aggarwal BB, Puri RK (eds) Human Cytokines: Their roles in disease and therapy. Cambridge, Massachusetts, USA; Blackwell Science 1995: 253
    Google Scholar
  • 30 Rohde T, McLean D A, Richter E A, Kiens B, Pedersen B K. Prolonged submaximal eccentric exercise is associated with increased levels of plasma IL-6.  Am J Physiol. 1997;  273 E85-E91
    PubMedGoogle Scholar
  • 31 Ross R. Atherosclerosis - An inflammatory disease.  New Engl J Med. 1999;  340 115-126
    CrossrefPubMedGoogle Scholar
  • 32 Sprenger H, Jacobs C, Nain M, Gressner A M, Prinz H, Wesemann W, Gemsa D. Enhanced release of cytokines, interleukin-2 receptors, and neopterin after long-distance running.  Clin Immunol Immunopathol. 1992;  63 188-195
    CrossrefPubMedGoogle Scholar
  • 33 Torres J M, Cardenas O, Vasquez A, Schlossberg D. Streptococcus pneumoniae bacteremia in a community hospital.  Chest. 1998;  113 387-390
    CrossrefPubMedGoogle Scholar
  • 34 Ullum H, Haahr P M, Diamant M, Palmo J, Halkjaer-Kristensen J, Pedersen B K. Bicycle exercise enhances plasma IL-6 but does not change IL-1α, IL-1β, IL-6, or TNFα pre-mRNA in BMNC.  J Appl Physiol. 1994;  77 93-97
    PubMedGoogle Scholar
  • 35 Vandenabeele P, Fiers W. Is amyloidogenesis during Alzheimer's disease due to an IL-1/IL-6 mediated 'acute phase response' in the brain?.  Immunology Today. 1991;  12 217-219
    CrossrefPubMedGoogle Scholar
  • 36 Waage A, Halstensen A, Shalaby R, Brandtæg P, Kierullf P, Espevik T. Local production of tumour necrosis factor-α, interleukin 1, and interleukin 6 in meningococcal meningitis.  J Exp Med. 1989;  170 1859-1867
    CrossrefPubMedGoogle Scholar
  • 37 Wei J, Xu H, Davies J L, Hemmings G P. Increase of plasma IL-6 concentration with age in healthy subjects.  Life Sci. 1992;  51 1953-1956
    CrossrefPubMedGoogle Scholar

Bente Klarlund Pedersen

Department of Infectious Diseases M7721 Rigshospitalet

Tagensvej 20 2200 Copenhagen N Denmark

Phone: Phone:+ 45-3545-7797

Fax: Fax:+ 45-3545-6648

Email: E-mail:bkp@rh.dk

      >