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Elevation of proinflammatory cytokines following intra\u2010articular fracture may lead to synovial catabolism and cartilage degradation. We aimed to compare cytokine levels in injured and healthy ankle joints, examine the longer\u2010term cytokine levels in fractured ankles, and investigate the association between cytokine levels in fractured ankles and plasma.\n                    <jats:italic>Materials and Methods.<\/jats:italic>\n                    In this cross\u2010sectional study, synovial fluid (SF) and plasma of forty\u2010seven patients with acute intra\u2010articular ankle fractures and eight patients undergoing implant removal were collected prior to surgery. We determined concentrations of sixteen inflammatory cytokines, two cartilage degradation proteins, and four metabolic proteins and compared the levels in acutely injured ankles with those of the healthy contralateral side or during metal removal. Cytokine levels in injured ankles were also compared to serum cytokine levels. Nonparametric Wilcoxon rank\u2010sum and Spearman tests were used for statistical analysis, and a\n                    <jats:italic>p<\/jats:italic>\n                    value below 0.05 was considered significant.\n                    <jats:italic>Results<\/jats:italic>\n                    . Compared to the healthy ankles, the synovial fluid in ankles with acute intra\u2010articular fracture had elevated levels of several proinflammatory cytokines and proteases (IL\u20101\n                    <jats:italic>\u03b2<\/jats:italic>\n                    , IL\u20102, IL\u20106, IL\u20108, IL\u201012p70, TNF, IFN\n                    <jats:italic>\u03b3<\/jats:italic>\n                    , MMP\u20101, MMP\u20103, and MMP\u20109) and anti\u2010inflammatory cytokines (IL\u20101RA, IL\u20104, IL\u201010, and IL\u201013). The levels of cartilage degradation products (ACG, CTX\u20102) and metabolic mediators (TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1 and TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    2) were also significantly higher. Synovial concentrations of ACG, IL\u201012\u2010p70, IFN\n                    <jats:italic>\u03b3<\/jats:italic>\n                    , IL\u20104, and bFGF correlated with serum levels. While most of the examined synovial cytokines were unchanged after implant removal, IL\u20104 and IL\u20106 levels were upregulated.\n                    <jats:italic>Conclusions<\/jats:italic>\n                    . We show that an acute ankle fracture is followed by an inflammatory reaction and cartilage degeneration. These data contribute to the current understanding of the protein regulation behind the development of PTOA and is a further step towards supplementing the current surgical treatment. This cross\u2010sectional study was \u201cretrospectively registered\u201d on the 31th October 2017 at ClinicalTrials.gov (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03769909\">NCT03769909<\/jats:ext-link>\n                    ). The registration was carried out after inclusion of the first patient and prior to finalization of patient recruitment and statistical analyses:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03769909?term=NCT03769909&amp;draw=2&amp;rank=1\">https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03769909?term=NCT03769909&amp;draw=2&amp;rank=1<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1155\/2021\/8897440","type":"journal-article","created":{"date-parts":[[2021,1,9]],"date-time":"2021-01-09T12:51:56Z","timestamp":1610196716000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Elevation of Inflammatory Cytokines and Proteins after Intra\u2010Articular Ankle Fracture: A Cross\u2010Sectional Study of 47 Ankle Fracture Patients"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5433-8312","authenticated-orcid":false,"given":"That Minh","family":"Pham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars Henrik","family":"Frich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9276-4902","authenticated-orcid":false,"given":"Kate Lykke","family":"Lambertsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6829-4787","authenticated-orcid":false,"given":"S\u00f8ren","family":"Overgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagen","family":"Schmal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,9]]},"reference":[{"key":"e_1_2_13_1_2","first-page":"44","article-title":"Epidemiology of ankle arthritis: report of a consecutive series of 639 patients from a tertiary orthopaedic center","volume":"25","author":"Saltzman C. 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