Study One: Acute Inflammatory Response to Stretching

  • Nikos C. Apostolopoulos


Stretching, defined as an external/internal force, is responsible for determining the range of motion (ROM) of the connective tissue [muscles, tendons, and the myotendon unit (MTU)]. The magnitude and rate of stretching may be responsible for inducing a mechanical response of the musculoskeletal system, such as trauma, or increases in ROM. Since mechanical forces provide fundamental physiological stimulus in living organisms, the degree of stretching intensity, such as low-intensity versus high-intensity stretching, may either optimise recovery from muscle damage by ameliorating inflammation or cause damage to tissue. This damage, in response to the stress placed on the tissue by stretching, may induce an inflammatory response. In this randomised crossover trial, 12 participants were exposed to both a high-intensity passive static stretch (discomfort with slight pain) and no stretch. In order to investigate whether high-intensity passive static stretching causes an inflammatory response, inflammatory blood biomarkers were measured [pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and hsCRP]. The right and left hamstrings, glutes, and quadriceps were passively stretched by a trained therapist. Each muscle group was stretched for three sets, held at 60 s each, at an intensity level of 8 out of 10, as measured by a numerical rating scale. The total time was 18 min. The study observed that an inflammatory response was associated with high-intensity passive static stretching when compared to no stretch.


  1. Abdel-Aziem, A. A., Draz, A. H., Mosaad, D. M., & Abdelraou, O. R. (2013). Effect of body position and type of stretching on hamstring flexibility. International Journal of Medical Research and Health Sciences, 2, 399–406.CrossRefGoogle Scholar
  2. Aghaeepour, N., Finak, G., The Flowcap Consortium, The Dream Consortium, Hoos, H., Mosmann, T. R., et al. (2013). Critical assessment of automated flow cytometry data analysis techniques. Nature Methods, 10, 228–238.CrossRefGoogle Scholar
  3. Akira, S., Hirano, T., Taga, T., & Kishimoto, T. (1990). Biology of multifunctional cytokines: IL-6 and related molecules (IL-1 and TNF). FASEB, 4, 2860–2867.CrossRefGoogle Scholar
  4. Akira, S., Taga, T., & Kishimoto, T. (1993). Interleukin-6 in biology and medicine. Advances in Immunology, 54, 1–78.CrossRefGoogle Scholar
  5. Apostolopoulos, N. (2010). microStretching-A practical approach for recovery and regeneration. New Studies in Athletics, 25, 81–97.Google Scholar
  6. Apostolopoulos, N., Metsios, G. S., Flouris, A. D., Koutedakis, Y., & Wyon, M. (2015). The relevance of stretch intensity and position - a systematic review. Frontiers in Psychology, 6, 1128.CrossRefGoogle Scholar
  7. Cannon, J. G., Evans, W. J., Hughes, V. A., Meredith, C. N., & Dinarello, C. A. (1986). Physiological mechanisms contributing to increased inteleukin-1 secretion. Journal of Applied Physiology, 61, 1869–1874.CrossRefGoogle Scholar
  8. Chatzinikolaou, A., Fatouros, I., Gourgoulis, V., Avloniti, A., Jamurtas, A. Z., Nikolaidis, M. G., et al. (2010). Time course of changes in performance and inflammatory responses after acute plyometric exercise. Journal of Strength and Conditioning Research, 24, 1389–1398.CrossRefGoogle Scholar
  9. Chiu, Y. H., Hou, S. K., How, C. K., Li, L. H., Kao, W. F., Yang, C. C., et al. (2013). Influence of a 100-km ultra-marathon on hepatitis B carrier runners. International Journal of Sports Medicine, 34, 841–845.CrossRefGoogle Scholar
  10. Cunniffe, B., Hore, A. J., Whitcombe, D. M., Jones, K. P., Baker, J. S., & Davies, B. (2010). Time course of changes in immunoendocrine markers following an international rugby game. European Journal of Applied Physiology, 108, 113–122.CrossRefGoogle Scholar
  11. Cunniffe, B., Hore, A. J., Whitcombe, D. M., Jones, K. P., Davies, B., & Baker, J. S. (2011). Immunoendocrine responses over a three week international rugby union series. The Journal of Sports Medicine and Physical Fitness, 51, 329–338.PubMedGoogle Scholar
  12. Fallon, K. E. (2001). The acute phase response and exercise: The ultramarathon as prototype exercise. Clinical Journal of Sport Medicine, 11, 38–43.CrossRefGoogle Scholar
  13. Febbraio, M. A., & Pedersen, B. K. (2002). Muscle-derived interleukin-6: Mechanisms for activation and possible biological roles. FASEB, 16, 1335–1347.CrossRefGoogle Scholar
  14. Frey, W., Wassmer, P., Frey-Rinddova, P., Braun, D., Schwarz, F., Arnold, M., et al. (1994). Muscle aches and biochemical changes following a ultra-marathon in the cold-modification by diclofenac. Schweizerische Zeitschrift für Medizin und Traumatologie, 2, 30–36.Google Scholar
  15. Gabay, C. (2006). Interleukin-6 and chronic inflammation. Arthritis Research & Therapy, 8, S3–S8.CrossRefGoogle Scholar
  16. Green, C. L., Brown, L., Stewart, J. J., Xu, Y., Litwin, V., & Mccloskey, T. W. (2011). Recommendations for the validation of flow cytometric testing during drug development: I instrumentation. Journal of Immunological Methods, 363, 104–119.CrossRefGoogle Scholar
  17. Guissard, N., & Duchateau, J. (2006). Neural aspects of muscle stretching. Exercise and Sport Sciences Reviews, 34, 154–158.CrossRefGoogle Scholar
  18. Jacobs, C. A., & Sciacia, A. D. (2011). Factors that influence the efficacy of stretching programs for patients with hypomobility. Sports Health, 3, 520–523.CrossRefGoogle Scholar
  19. Kasapis, C., & Thompson, P. D. (2005). The effects of physical activity on serum C-reactive protein and inflammatory markers. JACC, 45, 1563–1569.CrossRefGoogle Scholar
  20. Kilicarslan, A., Uysal, A., & Roach, E. C. (2013). Acute phase reactants. Acta Medica, 2, 2–7.Google Scholar
  21. Kim, H. J., Lee, Y. H., & Kim, C. K. (2007). Biomarkers of muscle and cartilage damage and inflammation during a 200 km run. European Journal of Applied Physiology, 99, 443–447.CrossRefGoogle Scholar
  22. Knudson, D. (2006). The biomechanics of stretching. Journal of Exercise Science & Physiotherapy, 2, 3–12.Google Scholar
  23. Kopf, M., Baumann, H., Freer, G., Freudenberg, M., Lamers, M., Kishimoto, T., et al. (1994). Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature, 368, 339–342.CrossRefGoogle Scholar
  24. Lund, A. J., Hurst, T. L., Tyrell, R. M., & Thompson, D. (2011). Markers of chronic inflammation with short-term changes in physical activity. Medicine & Science in Sports & Exercise, 43, 578–583.CrossRefGoogle Scholar
  25. Mackiewicz, A., Speroff, T., Ganapathi, M. K., & Kushner, I. (1991). Effects of cytokine combinations on acute phase protein production in two human hepatoma cell lines. Journal of Immunology, 146, 3032–3037.Google Scholar
  26. Marino, A., & Giotta, N. (2008). Cinacalcet, fetuin-A and interleukin-6. Nephrology, Dialysis, Transplantation, 23, 1461.Google Scholar
  27. Marnell, L., Mold, C., & Du Clos, T. W. (2005). C-reactive protein: Ligannds, receptors and role in inflammation. Clinical Immunology, 117, 104–111.CrossRefGoogle Scholar
  28. Marschall, F. (1999). Wie beinflussen unterschiedliche dehnintensitaten kurzfristig die veranderung der bewegungsreichweite? (Effects of different stretch-intensity on the acute change of range of motion). Deutsche Zeitschrift fur Sportmedizin, 50, 5–9.Google Scholar
  29. Mccaffery, M., & Beebe, A. (1989). Pain: Clinical manual for nursing practice. St. Louis, MO: CV Mosby.Google Scholar
  30. Mcclure, P., Blackburn, L., & Dusold, C. (1994). The use of splints in the treatment of joint stiffness: Biologic rationale and an algorithm for making clinical decisions. Physical Therapy, 74, 1101–1107.CrossRefGoogle Scholar
  31. Mcfarland-Mancini, M. M., Funk, H. M., Paluch, A. M., Zhou, M., Giridhar, P. V., Mercer, C. A., et al. (2010). Differences in wound healing in mice with deficiency of IL-6 versus IL-6 receptor. Journal of Immunology, 184, 7219–7228.CrossRefGoogle Scholar
  32. Merskey, H., & Bogduk, N. (1994). Classification of chronic pain. Seattle, WA: IASP Press.Google Scholar
  33. Moors, M. A., & Mizel, S. B. (2000). Proteasome-mediated regulation of interleukin-1beta turnover and export in human monocytes. Journal of Leukocyte Biology, 68, 131–136.PubMedGoogle Scholar
  34. Mujika, I., Chatard, J.-C., Busso, T., Geyssant, A., Barale, F., & Lacoste, L. (1995). The effects of training on performance in competitive swimming. Canadian Journal of Applied Physiology, 20, 395–406.CrossRefGoogle Scholar
  35. Nikolaou, P. K., Macdonald, B. L., Glisson, R. R., Seaber, A. V., & Garrett Jr., W. E. (1987). Biomechanical and histological evaluation of muscle after controlled strain injury. The American Journal of Sports Medicine, 15, 9–14.CrossRefGoogle Scholar
  36. Noakes, T. D. (1987). Effect of exercise on serum enzyme activities in humans. Sports Medicine, 4, 245–267.CrossRefGoogle Scholar
  37. O’Hara, D. M., Xu, Y., Liang, Z., Reddy, M. P., Wu, D. Y., & Litwin, V. (2011). Recommendations for the validation of flow cytometric testing during drug development: II assays. Journal of Immunological Methods, 363, 120–134.CrossRefGoogle Scholar
  38. Oliver, J. C., Bland, L. A., Oettinger, C. W., Arduino, M. J., Mcallister, S. K., Aquero, S. M., et al. (1993). Cytokine kinetics in an in vitro whole blood model following an endotoxin challenge. Lymphokine and Cytokine Research, 12, 115–120.PubMedGoogle Scholar
  39. Paulsen, G., Mikkelsen, U. R., Raastad, T., & Peake, J. M. (2012). Leukocytes, cytokines and satellite cells: What role do they play in muscle damage and regeneration following eccentric exercise? Exercise Immunology Review, 18, 42–97.PubMedGoogle Scholar
  40. Pearle, A. D., Scanzello, C. R., George, S., Mandl, L. A., Dicarlo, E., Peterson, M., et al. (2007). Elevated high-sensitivity C-reactive protein levels are associated with lack inflammatory findings in patients with osteoarthritis. Osteoarthritis and Cartilage, 15, 516–523.CrossRefGoogle Scholar
  41. Pepys, M. B., & Hirschfield, G. M. (2003). C-reactive protein: a critical update. The Journal of Clinical Investigation, 111, 1805–1812.CrossRefGoogle Scholar
  42. Petersen, A. M. W., & Pedersen, B. K. (2005). The anti-inflammatory effect of exercise. Journal of Applied Physiology, 98, 1154–1162.CrossRefGoogle Scholar
  43. Pradhan, A. D., Manson, J. E., Rifai, N., Buring, J. E., & Ridker, P. M. (2001). C-reactive protein, interleukin 6, and risk of developing type 2 diabetus mellitus. JAMA, 286, 327–334.CrossRefGoogle Scholar
  44. Prunet, C., Montange, T., Vejux, A., Laubriet, A., Rohmer, J.-F., Riedinger, J.-M., et al. (2006). Multiplexed flow cytometric analyses of pro- and anti-inflammatory cytokines in the culture media of oxysterol-treated human monocytic cells and in the sera of atherosclerotic patients. Cytometry Part A, 69A, 359–373.CrossRefGoogle Scholar
  45. Ramadori, G., Van Damme, J., Rieder, H., & Meyer Zum Buschenfelde, K. H. (1988). Interleukin 6, the third mediator of acute-phase reaction, modulates hepatic protein synthesis in human and mouse. Comparison with interleukin 1 beta and tumor necrosis factor-alpha. European Journal of Immunology, 18, 1259–1264.CrossRefGoogle Scholar
  46. Roberts, W. L., Moulton, L., Law, T. C., Farrow, G., Cooper-Anderson, M., Savory, J., et al. (2001). Evaluation of nine-automated high sensitivity C-reactive protein methods: Implications for clinical and epidemiological applications. Part 2. Clinical Chemistry, 47, 418–425.PubMedGoogle Scholar
  47. Siegel, A. J., Stec, J. J., Lipinska, I., Van Cott, E. M., Lewandrowski, K. B., Ridker, P. M., et al. (2001). Effect of marathon running on inflammatory and hemostatic markers. The American Journal of Cardiology, 88, 918–920.CrossRefGoogle Scholar
  48. Streetz, K. L., Wustefeld, T., Klein, C., Manns, M. P., & Trautwein, C. (2001). Mediators of inflammation and acute phase response in the liver. Cellular and Molecular Biology (Noisy-le-Grand, France), 47, 661–673.Google Scholar
  49. Taylor, C., Rogers, G., Goodman, C., Baynes, R. D., Bothwell, T. H., Bezwoda, W. R., et al. (1987). Hematologic, iron-related, and acute-phase protein responses to sustained strenuous exercise. Journal of Applied Physiology, 62, 464–469.CrossRefGoogle Scholar
  50. Taylor, D. C., Dalton, J. D., Seaber, A. V., & Garrett, W. E. (1990). Viscoelastic properties of muscle-tendon units. The biomechanical effects of stretching. American Journal of Sports Medicine, 18, 300–309.CrossRefGoogle Scholar
  51. Tidball, J. G. (1995). Inflammatory cell response to acute muscle injury. Medicine and Science in Sports and Exercise, 27, 1022–1032.CrossRefGoogle Scholar
  52. Vigushin, D. M., Pepys, M. B., & Hawkins, P. N. (1993). Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health and disease. The Journal of Clinical Investigation, 91, 1351–1357.CrossRefGoogle Scholar
  53. Weight, L. M., Alexander, D., & Jacobs, P. (1991). Strenuous exercise: Analogous to the acute-phase response? Clinical Science (London, England), 81, 677–683.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Nikos C. Apostolopoulos
    • 1
  1. 1.University of TorontoTorontoCanada

Personalised recommendations