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. 1993;2(5):335–342. doi: 10.1155/S0962935193000468

Inflammatory response to strenuous muscular exercise in man

G Camus 1,2,, G Deby-Dupont 4, C Deby 2, A Juchmès-Ferir 3, J Pincemail 2, M Lamy 2,4
PMCID: PMC2365428  PMID: 18475542

Abstract

Based on the humoral and cellular changes occurring during strenuous muscular work in humans, the concept of inflammatory response to exercise (IRE) is developed. The main indices of IRE consist of signs of an acute phase response, leucocytosis and leucocyte activation, release of inflammatory mediators, tissue damage and cellular infiltrates, production of free radicals, activation of complement, and coagulation and fibrinolytic pathways. Depending on exercise intensity and duration, it seems likely that muscle and/or associated connective tissue damage, contact system activation due to shear stress on endothelium and endotoxaemia could be the triggering mechanisms of IRE. Although this phenomenon can be considered in most cases as a physiological process associated with tissue repair, exaggerated IRE could have physiopathological consequences. On the other hand, the influence of several factors such as age, sex, training, hormonal status, nutrition, anti-inflammatory drugs, and the extent to which IRE could be a potential risk for subjects undergoing intense physical training require further study.

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Selected References

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  1. Amelink G. J., van der Wal W. A., Wokke J. H., van Asbeck B. S., Bär P. R. Exercise-induced muscle damage in the rat: the effect of vitamin E deficiency. Pflugers Arch. 1991 Oct;419(3-4):304–309. doi: 10.1007/BF00371111. [DOI] [PubMed] [Google Scholar]
  2. Babior B. M. The respiratory burst of phagocytes. J Clin Invest. 1984 Mar;73(3):599–601. doi: 10.1172/JCI111249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bosenberg A. T., Brock-Utne J. G., Gaffin S. L., Wells M. T., Blake G. T. Strenuous exercise causes systemic endotoxemia. J Appl Physiol (1985) 1988 Jul;65(1):106–108. doi: 10.1152/jappl.1988.65.1.106. [DOI] [PubMed] [Google Scholar]
  4. Bourey R. E., Santoro S. A. Interactions of exercise, coagulation, platelets, and fibrinolysis--a brief review. Med Sci Sports Exerc. 1988 Oct;20(5):439–446. [PubMed] [Google Scholar]
  5. Brock-Utne J. G., Gaffin S. L., Wells M. T., Gathiram P., Sohar E., James M. F., Morrell D. F., Norman R. J. Endotoxaemia in exhausted runners after a long-distance race. S Afr Med J. 1988 May 7;73(9):533–536. [PubMed] [Google Scholar]
  6. Camus G., Pincemail J., Deby-Dupont G., Deby C., Juchmès-Ferir A., Lamy M. Effects of methylprednisolone on exercise-induced increases of plasma levels of polymorphonuclear elastase and myeloperoxidase in man. Preliminary results. Mediators Inflamm. 1993;2(4):323–326. doi: 10.1155/S0962935193000456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Camus G., Pincemail J., Ledent M., Juchmès-Ferir A., Lamy M., Deby-Dupont G., Deby C. Plasma levels of polymorphonuclear elastase and myeloperoxidase after uphill walking and downhill running at similar energy cost. Int J Sports Med. 1992 Aug;13(6):443–446. doi: 10.1055/s-2007-1021295. [DOI] [PubMed] [Google Scholar]
  8. Camus G., Sondag D., Maggipinto J., Pincemail J., Plumier A. F., Feron F., Juchmes-Ferir A., Duchateau J., Lamy M., Deby-Dupont G. Mobilisation des leucocytes lors de l'exercice dynamique sous-maximum. Arch Int Physiol Biochim Biophys. 1991 Dec;99(6):419–423. [PubMed] [Google Scholar]
  9. Cannon J. G., Fielding R. A., Fiatarone M. A., Orencole S. F., Dinarello C. A., Evans W. J. Increased interleukin 1 beta in human skeletal muscle after exercise. Am J Physiol. 1989 Aug;257(2 Pt 2):R451–R455. doi: 10.1152/ajpregu.1989.257.2.R451. [DOI] [PubMed] [Google Scholar]
  10. Cannon J. G., Kluger M. J. Endogenous pyrogen activity in human plasma after exercise. Science. 1983 May 6;220(4597):617–619. doi: 10.1126/science.6836306. [DOI] [PubMed] [Google Scholar]
  11. Cannon J. G., Orencole S. F., Fielding R. A., Meydani M., Meydani S. N., Fiatarone M. A., Blumberg J. B., Evans W. J. Acute phase response in exercise: interaction of age and vitamin E on neutrophils and muscle enzyme release. Am J Physiol. 1990 Dec;259(6 Pt 2):R1214–R1219. doi: 10.1152/ajpregu.1990.259.6.R1214. [DOI] [PubMed] [Google Scholar]
  12. Davies K. J., Quintanilha A. T., Brooks G. A., Packer L. Free radicals and tissue damage produced by exercise. Biochem Biophys Res Commun. 1982 Aug 31;107(4):1198–1205. doi: 10.1016/s0006-291x(82)80124-1. [DOI] [PubMed] [Google Scholar]
  13. Demers L. M., Harrison T. S., Halbert D. R., Santen R. J. Effect of prolonged exercise on plasma prostaglandin levels. Prostaglandins Med. 1981 Apr;6(4):413–418. doi: 10.1016/0161-4630(81)90073-2. [DOI] [PubMed] [Google Scholar]
  14. Dillard C. J., Litov R. E., Savin W. M., Dumelin E. E., Tappel A. L. Effects of exercise, vitamin E, and ozone on pulmonary function and lipid peroxidation. J Appl Physiol Respir Environ Exerc Physiol. 1978 Dec;45(6):927–932. doi: 10.1152/jappl.1978.45.6.927. [DOI] [PubMed] [Google Scholar]
  15. Dinarello C. A. Interleukin-1 and the pathogenesis of the acute-phase response. N Engl J Med. 1984 Nov 29;311(22):1413–1418. doi: 10.1056/NEJM198411293112205. [DOI] [PubMed] [Google Scholar]
  16. Dufaux B., Order U. Complement activation after prolonged exercise. Clin Chim Acta. 1989 Jan 13;179(1):45–49. doi: 10.1016/0009-8981(89)90021-1. [DOI] [PubMed] [Google Scholar]
  17. Dufaux B., Order U., Liesen H. Effect of a short maximal physical exercise on coagulation, fibrinolysis, and complement system. Int J Sports Med. 1991 Jun;12 (Suppl 1):S38–S42. doi: 10.1055/s-2007-1024748. [DOI] [PubMed] [Google Scholar]
  18. Dufaux B., Order U. Plasma elastase-alpha 1-antitrypsin, neopterin, tumor necrosis factor, and soluble interleukin-2 receptor after prolonged exercise. Int J Sports Med. 1989 Dec;10(6):434–438. doi: 10.1055/s-2007-1024939. [DOI] [PubMed] [Google Scholar]
  19. Duthie G. G., Robertson J. D., Maughan R. J., Morrice P. C. Blood antioxidant status and erythrocyte lipid peroxidation following distance running. Arch Biochem Biophys. 1990 Oct;282(1):78–83. doi: 10.1016/0003-9861(90)90089-h. [DOI] [PubMed] [Google Scholar]
  20. Fantone J. C., Ward P. A. Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol. 1982 Jun;107(3):395–418. [PMC free article] [PubMed] [Google Scholar]
  21. Frei B., Stocker R., Ames B. N. Antioxidant defenses and lipid peroxidation in human blood plasma. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9748–9752. doi: 10.1073/pnas.85.24.9748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gohil K., Viguie C., Stanley W. C., Brooks G. A., Packer L. Blood glutathione oxidation during human exercise. J Appl Physiol (1985) 1988 Jan;64(1):115–119. doi: 10.1152/jappl.1988.64.1.115. [DOI] [PubMed] [Google Scholar]
  23. Hansen J. B., Wilsgård L., Olsen J. O., Osterud B. Formation and persistence of procoagulant and fibrinolytic activities in circulation after strenuous physical exercise. Thromb Haemost. 1990 Nov 30;64(3):385–389. [PubMed] [Google Scholar]
  24. Hansen J. B., Wilsgård L., Osterud B. Biphasic changes in leukocytes induced by strenuous exercise. Eur J Appl Physiol Occup Physiol. 1991;62(3):157–161. doi: 10.1007/BF00643735. [DOI] [PubMed] [Google Scholar]
  25. Haralambie G., Keul J. Serum glycoprotein levels in athletes in training. Experientia. 1970 Sep 26;26(9):959–960. doi: 10.1007/BF02114129. [DOI] [PubMed] [Google Scholar]
  26. Haralambie G. Serum glycoproteins and physical exercise. Clin Chim Acta. 1969 Nov;26(2):287–291. doi: 10.1016/0009-8981(69)90380-5. [DOI] [PubMed] [Google Scholar]
  27. Hasson S. M., Daniels J. C., Divine J. G., Niebuhr B. R., Richmond S., Stein P. G., Williams J. H. Effect of ibuprofen use on muscle soreness, damage, and performance: a preliminary investigation. Med Sci Sports Exerc. 1993 Jan;25(1):9–17. doi: 10.1249/00005768-199301000-00003. [DOI] [PubMed] [Google Scholar]
  28. Hellsten Y., Ahlborg G., Jensen-Urstad M., Sjödin B. Indication of in vivo xanthine oxidase activity in human skeletal muscle during exercise. Acta Physiol Scand. 1988 Sep;134(1):159–160. doi: 10.1111/j.1748-1716.1988.tb08475.x. [DOI] [PubMed] [Google Scholar]
  29. Herbaczynska-Cedro K., Staszewska-Barczak J., Janczewska H. Muscular work and the release of prostaglandin-like substances. Cardiovasc Res. 1976 Jul;10(4):413–420. doi: 10.1093/cvr/10.4.413. [DOI] [PubMed] [Google Scholar]
  30. Jackson M. J., Edwards R. H., Symons M. C. Electron spin resonance studies of intact mammalian skeletal muscle. Biochim Biophys Acta. 1985 Nov 20;847(2):185–190. doi: 10.1016/0167-4889(85)90019-9. [DOI] [PubMed] [Google Scholar]
  31. Jones D. A., Newham D. J., Round J. M., Tolfree S. E. Experimental human muscle damage: morphological changes in relation to other indices of damage. J Physiol. 1986 Jun;375:435–448. doi: 10.1113/jphysiol.1986.sp016126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Kanter M. M., Nolte L. A., Holloszy J. O. Effects of an antioxidant vitamin mixture on lipid peroxidation at rest and postexercise. J Appl Physiol (1985) 1993 Feb;74(2):965–969. doi: 10.1152/jappl.1993.74.2.965. [DOI] [PubMed] [Google Scholar]
  33. Kihlström M., Salminen A., Vihko V. Prednisolone decreases exercise-induced acid hydrolase response in mouse skeletal muscle. Eur J Appl Physiol Occup Physiol. 1984;53(1):53–56. doi: 10.1007/BF00964690. [DOI] [PubMed] [Google Scholar]
  34. Kokot K., Schaefer R. M., Teschner M., Gilge U., Plass R., Heidland A. Activation of leukocytes during prolonged physical exercise. Adv Exp Med Biol. 1988;240:57–63. doi: 10.1007/978-1-4613-1057-0_6. [DOI] [PubMed] [Google Scholar]
  35. Kuipers H., Keizer H. A., Verstappen F. T., Costill D. L. Influence of a prostaglandin-inhibiting drug on muscle soreness after eccentric work. Int J Sports Med. 1985 Dec;6(6):336–339. doi: 10.1055/s-2008-1025866. [DOI] [PubMed] [Google Scholar]
  36. Kushner I. The phenomenon of the acute phase response. Ann N Y Acad Sci. 1982;389:39–48. doi: 10.1111/j.1749-6632.1982.tb22124.x. [DOI] [PubMed] [Google Scholar]
  37. Liesen H., Dufaux B., Hollmann W. Modifications of serum glycoproteins the days following a prolonged physical exercise and the influence of physical training. Eur J Appl Physiol Occup Physiol. 1977 Dec 22;37(4):243–254. doi: 10.1007/BF00430954. [DOI] [PubMed] [Google Scholar]
  38. Maughan R. J., Donnelly A. E., Gleeson M., Whiting P. H., Walker K. A., Clough P. J. Delayed-onset muscle damage and lipid peroxidation in man after a downhill run. Muscle Nerve. 1989 Apr;12(4):332–336. doi: 10.1002/mus.880120412. [DOI] [PubMed] [Google Scholar]
  39. McCarthy D. A., Dale M. M. The leucocytosis of exercise. A review and model. Sports Med. 1988 Dec;6(6):333–363. doi: 10.2165/00007256-198806060-00002. [DOI] [PubMed] [Google Scholar]
  40. Northoff H., Berg A. Immunologic mediators as parameters of the reaction to strenuous exercise. Int J Sports Med. 1991 Jun;12 (Suppl 1):S9–15. doi: 10.1055/s-2007-1024743. [DOI] [PubMed] [Google Scholar]
  41. Nowak J., Wennmalm A. Effect of exercise on human arterial and regional venous plasma concentrations of prostaglandin E. Prostaglandins Med. 1978 Dec;1(6):489–497. doi: 10.1016/0161-4630(78)90119-2. [DOI] [PubMed] [Google Scholar]
  42. Pincemail J., Camus G., Roesgen A., Dreezen E., Bertrand Y., Lismonde M., Deby-Dupont G., Deby C. Exercise induces pentane production and neutrophil activation in humans. Effect of propranolol. Eur J Appl Physiol Occup Physiol. 1990;61(3-4):319–322. doi: 10.1007/BF00357620. [DOI] [PubMed] [Google Scholar]
  43. Rotto D. M., Massey K. D., Burton K. P., Kaufman M. P. Static contraction increases arachidonic acid levels in gastrocnemius muscles of cats. J Appl Physiol (1985) 1989 Jun;66(6):2721–2724. doi: 10.1152/jappl.1989.66.6.2721. [DOI] [PubMed] [Google Scholar]
  44. Round J. M., Jones D. A., Cambridge G. Cellular infiltrates in human skeletal muscle: exercise induced damage as a model for inflammatory muscle disease? J Neurol Sci. 1987 Dec;82(1-3):1–11. doi: 10.1016/0022-510x(87)90002-5. [DOI] [PubMed] [Google Scholar]
  45. Röcker L., Drygas W. K., Heyduck B. Blood platelet activation and increase in thrombin activity following a marathon race. Eur J Appl Physiol Occup Physiol. 1986;55(4):374–380. doi: 10.1007/BF00422736. [DOI] [PubMed] [Google Scholar]
  46. Salminen A., Kihlström M. Protective effect of indomethacin against exercise-induced injuries in mouse skeletal muscle fibers. Int J Sports Med. 1987 Feb;8(1):46–49. doi: 10.1055/s-2008-1025639. [DOI] [PubMed] [Google Scholar]
  47. Schaefer R. M., Kokot K., Heidland A., Plass R. Jogger's leukocytes. N Engl J Med. 1987 Jan 22;316(4):223–224. doi: 10.1056/NEJM198701223160418. [DOI] [PubMed] [Google Scholar]
  48. Singh A., Smoak B. L., Patterson K. Y., LeMay L. G., Veillon C., Deuster P. A. Biochemical indices of selected trace minerals in men: effect of stress. Am J Clin Nutr. 1991 Jan;53(1):126–131. doi: 10.1093/ajcn/53.1.126. [DOI] [PubMed] [Google Scholar]
  49. Sjödin B., Hellsten Westing Y., Apple F. S. Biochemical mechanisms for oxygen free radical formation during exercise. Sports Med. 1990 Oct;10(4):236–254. doi: 10.2165/00007256-199010040-00003. [DOI] [PubMed] [Google Scholar]
  50. Smith J. A., Telford R. D., Baker M. S., Hapel A. J., Weidemann M. J. Cytokine immunoreactivity in plasma does not change after moderate endurance exercise. J Appl Physiol (1985) 1992 Oct;73(4):1396–1401. doi: 10.1152/jappl.1992.73.4.1396. [DOI] [PubMed] [Google Scholar]
  51. Smith J. K., Chi D. S., Krish G., Reynolds S., Cambron G. Effect of exercise on complement activity. Ann Allergy. 1990 Oct;65(4):304–310. [PubMed] [Google Scholar]
  52. Smith L. L. Acute inflammation: the underlying mechanism in delayed onset muscle soreness? Med Sci Sports Exerc. 1991 May;23(5):542–551. [PubMed] [Google Scholar]
  53. 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 May;63(2):188–195. doi: 10.1016/0090-1229(92)90012-d. [DOI] [PubMed] [Google Scholar]
  54. Stebbins C. L., Carretero O. A., Mindroiu T., Longhurst J. C. Bradykinin release from contracting skeletal muscle of the cat. J Appl Physiol (1985) 1990 Oct;69(4):1225–1230. doi: 10.1152/jappl.1990.69.4.1225. [DOI] [PubMed] [Google Scholar]
  55. Sumida S., Tanaka K., Kitao H., Nakadomo F. Exercise-induced lipid peroxidation and leakage of enzymes before and after vitamin E supplementation. Int J Biochem. 1989;21(8):835–838. doi: 10.1016/0020-711x(89)90280-2. [DOI] [PubMed] [Google Scholar]
  56. Symons J. D., Theodossy S. J., Longhurst J. C., Stebbins C. L. Intramuscular accumulation of prostaglandins during static contraction of the cat triceps surae. J Appl Physiol (1985) 1991 Nov;71(5):1837–1842. doi: 10.1152/jappl.1991.71.5.1837. [DOI] [PubMed] [Google Scholar]
  57. Taylor C., Rogers G., Goodman C., Baynes R. D., Bothwell T. H., Bezwoda W. R., Kramer F., Hattingh J. Hematologic, iron-related, and acute-phase protein responses to sustained strenuous exercise. J Appl Physiol (1985) 1987 Feb;62(2):464–469. doi: 10.1152/jappl.1987.62.2.464. [DOI] [PubMed] [Google Scholar]
  58. Thomsen B. S., Rødgaard A., Tvede N., Hansen F. R., Steensberg J., Halkjaer Kristensen J., Pedersen B. K. Levels of complement receptor type one (CR1, CD35) on erythrocytes, circulating immune complexes and complement C3 split products C3d and C3c are not changed by short-term physical exercise or training. Int J Sports Med. 1992 Feb;13(2):172–175. doi: 10.1055/s-2007-1021251. [DOI] [PubMed] [Google Scholar]
  59. Viti A., Muscettola M., Paulesu L., Bocci V., Almi A. Effect of exercise on plasma interferon levels. J Appl Physiol (1985) 1985 Aug;59(2):426–428. doi: 10.1152/jappl.1985.59.2.426. [DOI] [PubMed] [Google Scholar]
  60. Warren J. A., Jenkins R. R., Packer L., Witt E. H., Armstrong R. B. Elevated muscle vitamin E does not attenuate eccentric exercise-induced muscle injury. J Appl Physiol (1985) 1992 Jun;72(6):2168–2175. doi: 10.1152/jappl.1992.72.6.2168. [DOI] [PubMed] [Google Scholar]
  61. Weight L. M., Alexander D., Jacobs P. Strenuous exercise: analogous to the acute-phase response? Clin Sci (Lond) 1991 Nov;81(5):677–683. doi: 10.1042/cs0810677. [DOI] [PubMed] [Google Scholar]
  62. Westing Y. H., Ekblom B., Sjödin B. The metabolic relation between hypoxanthine and uric acid in man following maximal short-distance running. Acta Physiol Scand. 1989 Nov;137(3):341–345. doi: 10.1111/j.1748-1716.1989.tb08762.x. [DOI] [PubMed] [Google Scholar]
  63. Wheeler M. E., Davis G. L., Gillespie W. J., Bern M. M. Physiological changes in hemostasis associated with acute exercise. J Appl Physiol (1985) 1986 Mar;60(3):986–990. doi: 10.1152/jappl.1986.60.3.986. [DOI] [PubMed] [Google Scholar]

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