Increase in immune activation, vascular endothelial growth factor and erythropoietin after an ultramarathon run at moderate altitude.
Abstract
The present study was performed to investigate the effects of exhaustive long lasting exercise at moderate altitude on the time course of serum immunomodulatory peptides, vascular endothelial growth factor (VEGF) and serum erythropoietin (EPO). Thirteen well trained runners participated at the Swiss Alpine Marathon of Davos (distance 67 km, altitude difference 2300 m). Interleukin-6 was significantly elevated in the first 2h after the run. In contrast, tumor necrosis factor-alpha and both soluble tumor necrosis factor-a receptors I and II were increased after exercise termination and showed sustained serum concentrations the following days. Neopterin, a serum marker for the activation of the cellular immune system, was increased until day two after the run. Immediately after the run VEGF was significantly elevated and further increased 2.4-fold until day five post exercise (p = 0.005). EPO was also increased after exercise but reached its maximum 2 h after the run (2-fold increase; p = 0.004) and decreased thereafter. The main findings of our study are that prolonged strenuous exercise at moderate altitude induced a significant long lasting increase in serum VEGF and EPO which was accompanied by an activation of the immune system.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Human studies have shown that aerobic exercise (AE) is associated with peripheral increases in VEGF and IGF-1 serum concentrations.
“Human studies have shown that AE is associated with peripheral increases in VEGF and IGF-1 serum concentrations (Schobersberger et al., 2000; Llorens-Martín et al., 2010), and both molecules are known to cross the blood brain barrier and interact with hippocampal cells (Ding et al., 2006; Tang et al., 2010).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Schobersberger et al., 2000
Cites
Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis
Shweiki, D., Itin, A., Soffer, D., & Keshet, E. (1992) · Nature · doi:10.1038/359843a0 · Cited by 4,617 · see citing works
The Biology of Vascular Endothelial Growth Factor
Ferrara, N., & Davis-Smyth, T. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.1.0287 · Cited by 4,540 · see citing works
The Biology of Vascular Endothelial Growth Factor
Ferrara, N. (1997) · Endocrine Reviews · doi:10.1210/er.18.1.4 · Cited by 1,225 · see citing works
Erythropoietin: structure, control of production, and function
JELKMANN, W. E. B. (1992) · Physiological Reviews · doi:10.1152/physrev.1992.72.2.449 · Cited by 1,167 · see citing works
Self-citationInterleukin 6 Induces the Expression of Vascular Endothelial Growth Factor
Cohen, T., Nahari, D., Weiss-Cerem, L., Neufeld, G., & Levi, B.-Z. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.2.736 · Cited by 1,038 · see citing works
Regulation of Vascular Endothelial Growth Factor Expression in Cultured Keratinocytes.
Frank, S., Hübner, G., Breier, G., Longaker, M. T., Greenhalgh, D. G., & Werner, S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.21.12607 · Cited by 764 · see citing works
Exercise‐induced increase in serum interleukin‐6 in humans is related to muscle damage.
Brüünsgaard, H., Galbo, H., Halkjær-Kristensen, J., Johansen, T., MacLean, D. A., & Pedersen, B. K. (1997) · The Journal of Physiology · doi:10.1113/jphysiol.1997.sp021972 · Cited by 455 · see citing works
Hypoxic stimulation of vascular endothelial growth factor expression in vitro and in vivo.
Minchenko, О. H., Bauer, T., Salceda, S., & Caro, J. (1994) · PubMed · Cited by 429 · see citing works
Immune response to heavy exertion
Nieman, D. C. (1997) · Journal of Applied Physiology · doi:10.1152/jappl.1997.82.5.1385 · Cited by 409 · see citing works
Rate of erythropoietin formation in humans in response to acute hypobaric hypoxia
Eckardt, K., Boutellier, U., Kurtz, A., Schopen, M., Koller, E. A., & Bauer, C. (1989) · Journal of Applied Physiology · doi:10.1152/jappl.1989.66.4.1785 · Cited by 309 · see citing works
Angiogenic growth factor mRNA responses in muscle to a single bout of exercise
Breen, E. C., Johnson, E. C., Wagner, H., Tseng, H. M., Sung, L. A., & Wagner, P. D. (1996) · Journal of Applied Physiology · doi:10.1152/jappl.1996.81.1.355 · Cited by 302 · see citing works
Drenth, J. P. H., Uum, S. H. M. V., van Deuren, M., Pesman, G. J., van der Ven‐Jongekrijg, J., & van der Meer, J. W. (1995) · Journal of Applied Physiology · doi:10.1152/jappl.1995.79.5.1497 · Cited by 294 · see citing works
Ullum, H., Haahr, P., Diamant, M., Palmo, J., Halkjær-Kristensen, J., & Pedersen, B. K. (1994) · Journal of Applied Physiology · doi:10.1152/jappl.1994.77.1.93 · Cited by 197 · see citing works
Enhanced release of cytokines, interleukin-2 receptors, and neopterin after long-distance running
Sprenger, H., Jacobs, C., Nain, M., Gressner, A. M., Prinz, H., Wesemann, W., & Gemsa, D. (1992) · Clinical Immunology and Immunopathology · doi:10.1016/0090-1229(92)90012-d · Cited by 195 · see citing works
VEGF gene expression is upregulated in electrically stimulated rat skeletal muscle
Hang, J., Kong, L., Gu, J., & Adair, T. H. (1995) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1995.269.5.h1827 · Cited by 145 · see citing works
Erythrocyte volume, plasma volume, and acid-base changes in exercise and heat dehydration
van Beaumont, W., Underkofler, S., & Beaumont, S. (1981) · Journal of Applied Physiology · doi:10.1152/jappl.1981.50.6.1255 · Cited by 136 · see citing works
Hypoxemia increases serum interleukin-6 in humans
Klausen, T. L., Olsen, N. V., Poulsen, T. D., et al. (1997) · European Journal of Applied Physiology · doi:10.1007/s004210050278 · Cited by 130 · see citing works
Schmidt, W., Eckardt, K., Hilgendorf, A., Strauch, S., & Bauer, C. (1991) · International Journal of Sports Medicine · doi:10.1055/s-2007-1024713 · Cited by 97 · see citing works
Influence of prolonged physical exercise on the erythropoietin concentration in blood
Schwandt, H.-J., Heyduck, B., Gunga, H.-C., & R�cker, L. (1991) · European Journal of Applied Physiology · doi:10.1007/bf00868079 · Cited by 83 · see citing works
Effect of physical exercise in hypobaric conditions on atrial natriuretic peptide secretion
Vuolteenaho, O. J., Koistinen, P., Martikkala, V., et al. (1992) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1992.263.3.r647 · Cited by 80 · see citing works
Ertel, W., Morrison, M. H., Ayala, A., & Chaudry, I. H. (1995) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1995.269.1.r160 · Cited by 75 · see citing works
Grad, S., Ertel, W., Keel, M. J. B., et al. (1998) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.1998.064 · Cited by 68 · see citing works
Increase in serum vascular endothelial growth factor levels during altitude training
Asano, Kaneoka, K., NOMURA, Asano, Sone, H., Tsurumaru, YAMASHITA, MATSUO, Suzuki, ※., & Okuda (1998) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.1998.0318e.x · Cited by 66 · see citing works
Koller, A., Mair, J., Schobersberger, W., et al. (1998) · PubMed · Cited by 66 · see citing works
Self-citationGunga, H., Kirsch, K., Röcker, L., et al. (1994) · Journal of Applied Physiology · doi:10.1152/jappl.1994.76.3.1068 · Cited by 53 · see citing works
Increased immune activation during and after physical Eexercise
Tilz, G. P., Domej, W., Diez‐Ruiz, A., Weiß, G., Brezinschek, R. I., Brezinschek, H. P., Hüttl, E., Pristautz, H., Wächter, H., & Fuchs, D. (1993) · Immunobiology · doi:10.1016/s0171-2985(11)80497-3 · Cited by 48 · see citing works
Self-citationVascular endothelial growth factor in exercising humans under different environmental conditions
Gunga, H., Kirsch, K. A., R�cker, L., et al. (1999) · European Journal of Applied Physiology · doi:10.1007/s004210050541 · Cited by 43 · see citing works
The effect of short and long duration exercise on serum erythropoietin concentrations
Klausen, T., Breum, L., Fogh‐Andersen, N., Bennett, P., & Hippe, E. (1993) · European Journal of Applied Physiology · doi:10.1007/bf00864217 · Cited by 25 · see citing works
Influence of an ultramarathon race at moderate altitude on coagulation and fibrinolysis
Schobersberger, W., Wirleitner, B., Puschendorf, B., et al. (1996) · Fibrinolysis and Proteolysis · doi:10.1016/s0268-9499(05)80074-8 · Cited by 23 · see citing works
Self-citationHeits, F., Katschinski, D. M., Wiedemann, G., et al. (1997) · International Journal of Oncology · doi:10.3892/ijo.10.2.333 · Cited by 18 · see citing works
Serum eythropoietin in athletes at moderate altitude
Berglund, B., Fleck, S. J., Kearney, J. T., et al. (1992) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/j.1600-0838.1992.tb00313.x · Cited by 12 · see citing works
Time Course of Neopterin and Cytokines After an Extreme Bicycle Race at Moderate Altitude
Deetjen, C., Mair, J. M., Herold, M., et al. (1997) · Pteridines · doi:10.1515/pteridines.1997.8.3.195 · Cited by 7 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
VEGF is necessary for exercise‐induced adult hippocampal neurogenesis
Fabel, K., Fabel, K., Tam, B., Kaufer, D., Baiker, A., Simmons, N., Kuo, C. J., & Palmer, T. D. (2003) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2003.03041.x · Cited by 861 · see citing works
The Antidepressive Effects of Exercise: A Meta-Analysis of Randomized Trials
Rethorst, C. D., Wipfli, B. M., & Landers, D. M. (2009) · Sports Medicine · doi:10.2165/00007256-200939060-00004 · Cited by 541 · see citing works
Heine, V. M., Zareno, J., Maslam, S., Joëls, M., & Lucassen, P. J. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.03951.x · Cited by 225 · see citing works
Kandola, A., Hendrikse, J., Lucassen, P. J., & Yücel, M. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00373 · Cited by 155 · see citing works
“Human studies have shown that AE is associated with peripheral increases in VEGF and IGF-1 serum concentrations (Schobersberger et al., 2000; Llorens-Martín et al., 2010), and both molecules are known to cross the blood brain barrier and interact with hippocampal cells (Ding et al., 2006; Tang et…”
Joggin’ the Noggin: Towards a Physiological Understanding of Exercise-Induced Cognitive Benefits
Stimpson, N. J., Davison, G., & Javadi, A.-H. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.03.018 · Cited by 134 · see citing works
- Authors
- Schobersberger, W., Hobisch-Hagen, P., Fries, D., Wiedermann, F., Rieder-Scharinger, J., Villiger, B., Frey, W., Herold, M., Fuchs, D., & Jelkmann, W.
- Affiliations
- Universität Innsbruck (AT)
- Hochgebirgsklinik Davos (CH)
- Schulthess-Klinik (CH)
- University of Lübeck (DE)
- Corresponding author
- Schobersberger, Wolfgang
- ORCID
- Venue
- Immunobiology
- Publisher
- Elsevier BV
- Published
- 2000-04
- Volume
- 201
- Issue
- 5
- Pages
- 611-620
- ISSN
- 0171-2985 (ISSN-L)
- OpenAlex
- W1991495056
- Cited by
- 83
- References
- 32
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 8 · 2020: 2 · 2019: 2 · 2018: 8 · 2017: 4 · 2016: 3 · 2015: 5 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Immunobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medac
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › High Altitude and Hypoxia
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- ultramarathon, moderate altitude, exercise immunology, immune activation, vascular endothelial growth factor, erythropoietin, interleukin-6, TNF-α, soluble TNF receptors, neopterin, immunomodulatory peptides, endurance exercise
- MeSH terms
- Adult, Altitude, Blood Cell Count, Erythropoietin, Humans, Immune System, Lymphokines, Male, Middle Aged, Plasma Volume, Running, Time Factors, Tumor Necrosis Factor-alpha, Exercise, Interleukin-6, Cytokines, Endothelial Growth Factors, Receptors, Tumor Necrosis Factor, Neopterin, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
