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Int J Sports Med 2006; 27(9): 751-758
DOI: 10.1055/s-2005-872909
Immunology

© Georg Thieme Verlag KG Stuttgart · New York

The Response of the Novel Pro-Inflammatory Molecules S100A8/A9 to Exercise

F. C. Mooren1 , A. Lechtermann1 , M. Fobker3 , B. Brandt3 , C. Sorg2 , K. Völker1 , W. Nacken2
  • 1Institute of Sports Medicine, Muenster University Hospital, Muenster, Germany
  • 2Institute of Experimental Dermatology, Muenster University Hospital, Muenster, Germany
  • 3Institute of Clinical Chemistry and Laboratory Medicine, Muenster University Hospital, Muenster, Germany
Further Information

Publication History

Accepted after revision: July 15, 2005

Publication Date:
24 November 2005 (online)

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Abstract

Exercise shares many similarities with the acute phase response of inflammatory diseases. Recently, elevated serum levels of the novel pro-inflammatory molecules of the S100 protein family, S100A8 and S100A9, have been associated with various inflammatory diseases. The present study was conducted to assess their potential roles as inflammatory markers in monitoring the exercise-induced immune response. Seventeen male subjects of different training status performed a marathon run. Furthermore 13 subjects (10 male, 3 female) performed three different treadmill tests: strenuous (STE), moderate (MTE), and downhill (DTE). S100A8/A9 complexes were measured by ELISA, while white blood cell count (WBC) and C-reactive protein (CRP) were used as markers of the inflammatory response. Serum creatine kinase (CK) concentration was determined as a marker for muscle damage. After marathon S100A8/A9 increased dramatically during the early post-exercise period and returned to resting levels one day after the run. A similar pattern was found for WBC, while CK and CRP reached their maximum on the day after the run. Moreover, S100A8/A9 release was higher in the subgroup of well-trained athletes. The kinetic of the S100A8/A9 release after the treadmill tests depended on exercise intensity and was prolonged after eccentric exercise. In summary, the present results indicate that the novel pro-inflammatory molecules S100A8/A9 are very early and sensitive markers of the exercise-induced inflammatory response. Further investigations are necessary to evaluate the applicability of S100A8/A9 for monitoring the training process and to elucidate the dependence on training status.

Key words

Acute phase reaction - leucocytosis - treadmill - marathon - inflammation

References

  • 1 Berger D, Bölke E, Seidelmann M, Beger H G. Time-scale of interleukin-6, myeloid related proteins (MRP), c-reactive protein, and endotoxin plasma levels during the postoperative acute phase reaction.  Shock. 1997;  7 422-426
    CrossrefPubMedGoogle Scholar
  • 2 Berntzen H B, Munthe E, Fagerhol M K. A longitudinal study of the leukocyte protein L1 as an indicator of disease activity in patients with rheumatoid arthritis.  J Rheumatol. 1989;  16 1416-1420
    PubMedGoogle Scholar
  • 3 Brandtzaeg P, Gabrielsen T O, Dale I, Muller F, Steinbakk M, Fagerhol M K. The leucocyte protein L1 (calprotectin): a putative nonspecific defence factor at epithelial surfaces.  Adv Exp Med Biol. 1995;  371 201-206
    PubMedGoogle Scholar
  • 4 Brun J G, Jonsson R, Haga H J. Measurement of plasma calprotectin as an indicator of arthritis and disease activity in patients with inflammatory rheumatic diseases.  J Rheumatol. 1994;  21 733-738
    PubMedGoogle Scholar
  • 5 Burmeister G, Gallacchi G. A selective method for determining MRP8 and MRP14 homocomplexes and heterokomplexes by sandwich ELISA for the discrimination of active and non-active osteoarthritis from rheumatoid arthritis in sera and synovial fluid.  Immunpharmacol. 1995;  3 221-230
    PubMedGoogle Scholar
  • 6 Bury T B, Pirnay F. Effect of prolonged exercise on neutrophil myeloperoxidase secretion.  Int J Sports Med. 1995;  16 410-412
    PubMedGoogle Scholar
  • 7 Caimi G, Assennato P, Canino B, Montana M, Ventimiglia G, Lo Presti R. Exercise test: trend of the leukocyte flow properties, polymorphonuclear membrane fluidity and cytosolic Ca2+ content in normals, in subjects with previous acute myocardial infarction and in subjects with aortocoronary by-pass.  Clin Hemorrheol Microcirc. 1997;  17 127-135
    PubMedGoogle Scholar
  • 8 Camus G, Nys M, Poortmans J R, Venneman I, Monfils T, Deby-Dupont G, Juchmes-Ferir A, Deby C, Lamy M, Duchateau J. Endotoxaemia, production of tumour necrosis factor alpha and polymorphonuclear neutrophil activation following strenuous exercise in humans.  Eur J Appl Physiol. 1998;  79 62-68
    CrossrefPubMedGoogle 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 Criswell D S, Henry K M, Dimarco N M, Grossie V B. Chronic exercise and the pro-inflammatory response to endotoxin in the serum and heart.  Immunol Lett. 2004;  95 213-220
    CrossrefPubMedGoogle Scholar
  • 11 Dill D B, Costill D L. Calculation of percentage changes in volumes of blood plasma and red cells in dehydration.  J Appl Physiol. 1974;  37 247-248
    CrossrefPubMedGoogle Scholar
  • 12 Duclos M, Gouarne C, Bonnemaison D. Acute and chronic effects of exercise on tissue sensitivity to glucocorticoids.  J Appl Physiol. 2003;  94 869-875
    CrossrefPubMedGoogle Scholar
  • 13 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
  • 14 Fleshner M, Nguyen K T, Cotter C S, Watkins L R, Maier S F. Acute stressor exposure both suppresses acquired immunity and potentiates innate immunity.  Am J Physiol. 1998;  275 870-878
    PubMedGoogle Scholar
  • 15 Frosch M, Strey A, Vogl T, Wulffraat N M, Kuis W, Sunderkotter C, Harms E, Sorg C, Roth J. Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis.  Arthritis Rheum. 2000;  43 628-637
    CrossrefPubMedGoogle Scholar
  • 16 Haga H J, Brun I G, Berntzen H B, Cervera R, Khamashta M, Hughes G R. Calprotectin in patients with systemic lupus erythematosus: relation to clinical and laboratory parameters of disease activity.  Lupus. 1993;  2 47-50
    PubMedGoogle Scholar
  • 17 Hetland G, Talgo G J, Fagerhol M K. Chemotaxins C5a and fMLP induce release of calprotectin (leucocyte L1 protein) from polymorphonuclear cells in vitro.  Mol Pathol. 1998;  51 143-148
    PubMedGoogle Scholar
  • 18 Inui A. Cytokines and sickness behavior: implications from knockout animal models.  Trends Immunol. 2001;  22 469-473
    CrossrefPubMedGoogle Scholar
  • 19 Jeukendrup A E, Vet-joop K, Sturk A, Stegen J H, Senden J, Saris W H, Wagenmakers A J. Relationship between gastro-intestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and after a long-distance triathlon in highly trained men.  Clin Sci. 2000;  98 47-55
    CrossrefPubMedGoogle Scholar
  • 20 Jilma B, Dirnberger E, Loscher I, Rumplmayr A, Hildebrandt J, Eichler H G, Kapiotis S, Wagner O F. Menstrual cycle-associated changes in blood levels of interleukin-6, alpha1 acid glycoprotein, and C-reactive protein.  J Lab Clin Med. 1997;  130 69-75
    CrossrefPubMedGoogle Scholar
  • 21 Kane D, Roth J, Frosch M, Vogl T, Bresnihan B, Fitzgerald O. Increased perivascular synovial membrane expression of myeloid-related proteins in psoriatic arthritis.  Arthritis Rheum. 2003;  48 1676-1685
    CrossrefPubMedGoogle Scholar
  • 22 Kuruto R, Nozawa R, Takeishi K, Arai K, Yokota T, Takasaki Y. Myeloid calcium binding proteins: expression in the differentiated HL‐60 cells and detection in sera of patients with connective tissue diseases.  J Biochem. 1990;  108 650-653
    PubMedGoogle Scholar
  • 23 Miles B A, Lafuse W P, Zwilling B S. Binding of alpha-adrenergic receptors stimulates the anti-mycobacterial activity of murine peritoneal macrophages.  J Neuroimmunol. 1996;  71 19-24
    CrossrefPubMedGoogle Scholar
  • 24 Mooren F C, Lechtermann A, Fromme A, Thorwesten L, Volker K. Alterations in intracellular calcium signaling of lymphocytes after exhaustive exercise.  Med Sci Sports Exerc. 2001;  33 242-248
    PubMedGoogle Scholar
  • 25 Mooren F C, Lechtermann A, Volker K. Exercise-induced apoptosis of lymphocytes depends on training status.  Med Sci Sports Exerc. 2004;  36 1476-1483
    CrossrefPubMedGoogle Scholar
  • 26 Nacken W, Roth J, Sorg C, Kerkhoff C. S100A9/S100A8: Myeloid representatives of the S100 protein family as prominent players in innate immunity.  Microsc Res Tech. 2003;  60 569-580
    CrossrefPubMedGoogle Scholar
  • 27 Nacken W, Sopalla C, Propper C, Sorg C, Kerkhoff C. Biochemical characterization of the murine S100A9 (MRP14) protein suggests that it is functionally equivalent to its human counterpart despite its low degree of sequence homology.  Eur J Biochem. 2000;  267 560-565
    CrossrefPubMedGoogle Scholar
  • 28 Northoff H, Berg A. Immunologic mediators as parameters of the reaction to strenuous exercise.  Int J Sports Med. 1991;  12 9-15
    PubMedGoogle Scholar
  • 29 Pedersen B K, Kappel M, Klokker M. Possible roles of stress hormones in exercise-induced immunomodulation. Pedersen BK. Exercise Immunology. Austin, Texas; Landes Company 1997: 39-60
    Google Scholar
  • 30 Radak Z, Naito H, Kanek H, Tahara S, Nakamoto H, Takahashi R, Cardozo-Pelaez F, Goto S. Exercise training decreases DNA damage and increases DNA repair and resistance against oxidative stress of proteins in aged rat skeletal muscle.  Pflugers Arch. 2002;  445 273-278
    PubMedGoogle Scholar
  • 31 Ryckman C, Vandal K, Rouleau M, Talbot M, Tessier P A. Proinflammatory activities of S100: proteins S100A8, S100A9, and S100A8/A9 induce neutrophil chemotaxis and adhesion.  J Immunol. 2003;  170 3233-3242
    PubMedGoogle Scholar
  • 32 Severson J A, Fell R D, Tuig J G, Griffith D R. Adrenocortical function in aging exercise-trained rats.  J Appl Physiol. 1977;  43 839-843
    PubMedGoogle Scholar
  • 33 Starkie R, Ostrowski S R, Jauffred S, Febbraio M, Pedersen B K. Exercise and IL‐6 infusion inhibit endotoxin-induced TNF-alpha production in humans.  FASEB J. 2003;  17 884-886
    PubMedGoogle Scholar
  • 34 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-alpha levels after prolonged running.  Am J Physiol. 2001;  280 769-774
    PubMedGoogle Scholar
  • 35 Thorey I S, Roth J, Regenbogen J, Halle J P, Bittner M, Vogl T, Kaesler S, Bugnon P, Reitmaier B, Durka S, Graf A, Wockner M, Rieger N, Konstantinow A, Wolf E, Goppelt A, Werner S. The Ca2+-binding proteins S100A8 and S100A9 are encoded by novel injury-regulated genes.  J Biol Chem. 2001;  276 35818-35825
    CrossrefPubMedGoogle Scholar
  • 36 Vogl T, Ludwig S, Goebeler M, Strey A, Thorey I S, Reichelt R, Foell D, Gerke V, Nacken W, Werner S, Sorg C, Roth J. MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes.  Blood. 2004;  104 4260-4268
    CrossrefPubMedGoogle Scholar
  • 37 Weight L M, Alexander D, Jacobs P. Strenuous exercise: analogous to the acute-phase response?.  Clin Sci. 1991;  81 677-683
    CrossrefPubMedGoogle Scholar

F. C. Mooren

Institute of Sports Medicine · Muenster University Hospital

Horstmarer Landweg 39

48129 Muenster

Germany

Phone: + 492518335388

Fax: + 49 25 18 33 53 87

Email: mooren@uni-muenster.de

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