{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:06:14Z","timestamp":1791993974461,"version":"4.4.0"},"reference-count":49,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ultramarathon running elicits a profound inflammatory response, characterized by significant increases in interleukin-6 (IL-6) and C-reactive protein (CRP), with comparatively modest changes in tumor necrosis factor-alpha (TNF-\u03b1). We reviewed approximately 80 field studies of ultramarathon events (distances &gt;42.2 km) that measured IL-6, CRP, and TNF-\u03b1 before and after races. IL-6 typically spiked immediately post-race\u2014often rising dozens or even thousands of times above baseline\u2014then rapidly declined, usually returning to near baseline within 24\u201348 h. CRP, an acute-phase protein, exhibited a slower, sustained elevation, peaking 24\u201372 h after race completion and remaining above baseline for 2\u20133 days before gradually returning to normal. TNF-\u03b1 responses were variable: some studies reported small but significant post-race increases (roughly 1.2\u20131.7-fold above baseline), while others found no significant change in circulating TNF-\u03b1 despite the extreme effort. Longer race durations and distances generally correlated with higher peak IL-6 and CRP levels. Experienced ultramarathon runners tended to exhibit attenuated inflammatory responses compared with less-trained individuals, and anti-inflammatory cytokines (e.g., IL-10) increased in tandem with IL-6 in well-trained athletes, helping to mitigate TNF-\u03b1 elevations. In total, 28 studies were included in the final synthesis, and their quality was assessed using the Newcastle\u2013Ottawa Scale. Visual synthesis tools, including a PRISMA flowchart and time course plots, are provided to enhance the narrative\u2019s interpretability. In summary, ultramarathon running elicits a robust systemic inflammatory response with distinct temporal patterns for IL-6, CRP, and TNF-\u03b1. These findings have important implications for athlete recovery, monitoring, and understanding the physiological limits of the inflammatory response to extreme endurance stress.<\/jats:p>","DOI":"10.3390\/ijms26136317","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T06:56:54Z","timestamp":1751353014000},"page":"6317","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Inflammatory Response to Ultramarathon Running: A Review of IL-6, CRP, and TNF-\u03b1"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4885-6417","authenticated-orcid":false,"given":"Zbigniew","family":"Wa\u015bkiewicz","sequence":"first","affiliation":[{"name":"Institute of Sport Science, Jerzy Kukuczka Academy of Physical Education in Katowice, 40-065 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7435-9022","authenticated-orcid":false,"given":"Zhassyn","family":"Mukhambet","sequence":"additional","affiliation":[{"name":"Department of Sport Education and Coaching, Academy of Physical Education and Mass Sport, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daulet","family":"Azerbayev","sequence":"additional","affiliation":[{"name":"Department of Sport Education and Coaching, Academy of Physical Education and Mass Sport, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei","family":"Bondarev","sequence":"additional","affiliation":[{"name":"Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/00042752-200101000-00007","article-title":"The Acute Phase Response and Exercise: The Ultramarathon as Prototype Exercise","volume":"11","author":"Fallon","year":"2001","journal-title":"Clin. 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