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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
