{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:13:10Z","timestamp":1792789990978,"version":"4.5.0"},"reference-count":16,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Sciences, University of Balamand","id":[{"id":"https:\/\/ror.org\/01xvwxv41","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01xvwxv41","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Introduction: Inflammation is a central component of the biological processes involved in orthopedic interventions, whether performed for acute traumatic injuries or chronic non-traumatic conditions. Cytokines play major roles in modulating these responses; however, data describing cytokine activity in bone marrow, particularly during orthopedic procedures, remain limited. This study aimed to examine variations in cytokine levels in traumatic and non-traumatic orthopedic surgeries by analyzing simultaneous bone marrow and plasma samples. Methods: This single-center prospective observational study with exploratory objectives included skeletally mature patients undergoing urgent surgery for acute traumatic fractures or planned surgery for chronic non-traumatic degenerative orthopedic conditions. Bone-marrow and peripheral plasma samples were collected simultaneously intraoperatively. All samples were tested in duplicate for interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-4 (IL-4), interleukin-1 receptor antagonist (IL-1RA), and tumor necrosis factor-\u03b1 (TNF-\u03b1) using developmental ELISA kits. Cytokine levels were compared between traumatic and non-traumatic groups and between bone-marrow and plasma samples. Results: Nineteen participants were included, providing 19 bone-marrow samples and 15 plasma samples, with the number of available measurements varying among cytokines. Bone-marrow IL-10 was detected in three of five available traumatic samples and in none of the eight available non-traumatic samples (unadjusted p = 0.035; false-discovery-rate-adjusted q = 0.178). Plasma IL-1RA concentrations were higher in traumatic than in non-traumatic patients (median 2828.00 versus 1269.00 pg\/mL; unadjusted p = 0.038; q = 0.178). Bone-marrow IL-8 also showed higher concentrations in traumatic patients and approached the unadjusted significance threshold (p = 0.053; q = 0.178). No comparison remained statistically significant after FDR correction. Discussion: Bone-marrow IL-10 detection and plasma IL-1RA concentrations showed nominal between-group differences that did not remain statistically significant after multiple-comparison adjustment. Although preliminary and hypothesis-generating, these observations identify potentially informative local and systemic cytokine patterns and highlight the value of further investigating bone-marrow cytokine responses in orthopedic trauma.<\/jats:p>","DOI":"10.3390\/pathophysiology33030071","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:09:35Z","timestamp":1790075375000},"page":"71","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory Analysis of Bone Marrow IL-10 and Plasma IL-1RA in Acute Traumatic Versus Chronic Non-Traumatic Orthopedic Patients: A Prospective Observational Study"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1868-8811","authenticated-orcid":false,"given":"Muriel Tahtouh","family":"Zaatar","sequence":"first","affiliation":[{"name":"Department of Biological and Physical Sciences, American University in Dubai, Dubai P.O. Box 28282, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0119-7343","authenticated-orcid":false,"given":"Alex","family":"Kattoura","sequence":"additional","affiliation":[{"name":"School of Medicine and Medical Sciences, Holy Spirit University of Kaslik (USEK), Jounieh P.O. Box 446, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]},{"given":"Bayan","family":"Aasar","sequence":"additional","affiliation":[{"name":"Faculty of Sciences, University of Balamand, Al-Kourah, Tripoli P.O. Box 100, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Rima","family":"Othman","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine and Critical Care, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6918-5689","authenticated-orcid":false,"given":"Souheil","family":"Hallit","sequence":"additional","affiliation":[{"name":"School of Medicine and Medical Sciences, Holy Spirit University of Kaslik (USEK), Jounieh P.O. Box 446, Lebanon"},{"name":"Department of Psychology, College of Humanities, Effat University, Jeddah 21478, Saudi Arabia"},{"name":"Applied Science Research Center, Applied Science Private University, P.O. Box 166, Amman 11931, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Marc","family":"Karam","sequence":"additional","affiliation":[{"name":"Faculty of Sciences, University of Balamand, Al-Kourah, Tripoli P.O. Box 100, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6502-3110","authenticated-orcid":false,"given":"Ziad","family":"Fajloun","sequence":"additional","affiliation":[{"name":"Department of Cell Culture, Laboratory of Applied Biotechnology (LBA3B), Azm Center for Research in Biotechnology and Its Applications, EDST, Lebanese University, Tripoli P.O. Box 100, Lebanon"},{"name":"Faculty of Sciences 3, Lebanese University, Michel Slayman Tripoli Campus, Ras Maska 1352, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4595-1104","authenticated-orcid":false,"given":"Rabih","family":"Roufayel","sequence":"additional","affiliation":[{"name":"College of Engineering and Technology, American University of the Middle East, Egaila 54200, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Ramy","family":"Haroun","sequence":"additional","affiliation":[{"name":"School of Medicine and Medical Sciences, Holy Spirit University of Kaslik (USEK), Jounieh P.O. Box 446, Lebanon"},{"name":"Department of Orthopedic Surgery, Notre Dame de Secours University Hospital Center, Byblos P.O. Box 3, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Rita","family":"Khalil","sequence":"additional","affiliation":[{"name":"School of Medicine and Medical Sciences, Holy Spirit University of Kaslik (USEK), Jounieh P.O. Box 446, Lebanon"},{"name":"Department of Orthopedic Surgery, Notre Dame de Secours University Hospital Center, Byblos P.O. Box 3, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Boutros","family":"Tannoury","sequence":"additional","affiliation":[{"name":"School of Medicine and Medical Sciences, Holy Spirit University of Kaslik (USEK), Jounieh P.O. Box 446, Lebanon"},{"name":"Department of Orthopedic Surgery, Notre Dame de Secours University Hospital Center, Byblos P.O. Box 3, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9310-2060","authenticated-orcid":false,"given":"Francis","family":"Kattoura","sequence":"additional","affiliation":[{"name":"Aspetar Orthopaedic and Sports Medicine Hospital, Doha P.O. Box 29222, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Majd El Hajj","family":"Moussa","sequence":"additional","affiliation":[{"name":"School of Medicine and Medical Sciences, Holy Spirit University of Kaslik (USEK), Jounieh P.O. Box 446, Lebanon"},{"name":"Department of Orthopedic Surgery, Notre Dame de Secours University Hospital Center, Byblos P.O. Box 3, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Jean-Claude","family":"Lahoud","sequence":"additional","affiliation":[{"name":"School of Medicine and Medical Sciences, Holy Spirit University of Kaslik (USEK), Jounieh P.O. Box 446, Lebanon"},{"name":"Department of Orthopedic Surgery, Notre Dame de Secours University Hospital Center, Byblos P.O. Box 3, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Charbel","family":"Tawk","sequence":"additional","affiliation":[{"name":"School of Medicine and Medical Sciences, Holy Spirit University of Kaslik (USEK), Jounieh P.O. Box 446, Lebanon"},{"name":"Department of Orthopedic Surgery, Notre Dame de Secours University Hospital Center, Byblos P.O. Box 3, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Fadi","family":"Hoyek","sequence":"additional","affiliation":[{"name":"School of Medicine and Medical Sciences, Holy Spirit University of Kaslik (USEK), Jounieh P.O. Box 446, Lebanon"},{"name":"Department of Orthopedic Surgery, Notre Dame de Secours University Hospital Center, Byblos P.O. Box 3, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1007\/s00264-013-2261-2","article-title":"Cytokine Levels (IL-4, IL-6, IL-8 and TGF\u03b2) as Potential Biomarkers of Systemic Inflammatory Response in Trauma Patients","volume":"38","author":"Volpin","year":"2014","journal-title":"Int. Orthop."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1007\/s00068-023-02388-5","article-title":"Traumatic inflammatory response: Pathophysiological role and clinical value of cytokines","volume":"50","author":"Li","year":"2024","journal-title":"Eur. J. Trauma Emerg. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1302\/0301-620X.90B3.19688","article-title":"Stimulation of the local femoral inflammatory response to fracture and intramedullary reaming: A preliminary study of the source of the second hit phenomenon","volume":"90-B","author":"Morley","year":"2008","journal-title":"J. Bone Jt. Surg. Br."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.jcot.2018.08.004","article-title":"Impact of monocytic cytokines in polytrauma patients with orthopedics injures","volume":"10","author":"Sharma","year":"2019","journal-title":"J. Clin. Orthop. Trauma"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"478","DOI":"10.2106\/JBJS.N.00200","article-title":"Inflammatory Cytokine Response Following Acute Tibial Plateau Fracture","volume":"97","author":"Haller","year":"2015","journal-title":"J. Bone Jt. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1002\/jor.25183","article-title":"Inflammatory cytokines associated with outcomes in orthopedic trauma patients independent of New Injury Severity score: A pilot prospective cohort study","volume":"40","author":"Aneja","year":"2022","journal-title":"J. Orthop. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/j.joca.2015.08.015","article-title":"Inflammation in joint injury and post-traumatic osteoarthritis","volume":"23","author":"Lieberthal","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Iversen, I.J., Pham, T.M., and Schmal, H. (2021). Do acute inflammatory cytokines affect 3- and 12-month postoperative functional outcomes\u2013a prospective cohort study of 12 patients with proximal tibia fractures. BMC Musculoskelet. Disord., 22.","DOI":"10.1186\/s12891-021-04207-7"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1210\/endo.133.6.8243274","article-title":"Exposure to physical and psychological stressors elevates plasma interleukin 6: Relationship to the activation of hypothalamic-pituitary-adrenal axis","volume":"133","author":"Zhou","year":"1993","journal-title":"Endocrinology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S8756-3282(03)00086-3","article-title":"Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease","volume":"33","author":"Bendre","year":"2003","journal-title":"Bone"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Patilas, C., Varsamos, I., Galanis, A., Vavourakis, M., Zachariou, D., Marougklianis, V., Kolovos, I., Tsalimas, G., Karampinas, P., and Kaspiris, A. (2024). The Role of Interleukin-10 in the Pathogenesis and Treatment of a Spinal Cord Injury. Diagnostics, 14.","DOI":"10.3390\/diagnostics14020151"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Pham, T.M., Erichsen, J.L., Kowal, J.M., Overgaard, S., and Schmal, H. (2021). Elevation of Pro-Inflammatory Cytokine Levels Following Intra-Articular Fractures\u2014A Systematic Review. Cells, 10.","DOI":"10.20944\/preprints202103.0383.v1"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Meert, L., Mertens, M.G., Meeus, M., Vervullens, S., Baert, I., Beckw\u00e9e, D., Verdonk, P., and Smeets, R.J. (2023). Identification of Metabolic Factors and Inflammatory Markers Predictive of Outcome after Total Knee Arthroplasty in Patients with Knee Osteoarthritis: A Systematic Review. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20105796"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1084\/jem.179.5.1695","article-title":"Interleukin 10 (IL-10) upregulates IL-1 receptor antagonist production from lipopolysaccharide-stimulated human polymorphonuclear leukocytes by delaying mRNA degradation","volume":"179","author":"Cassatella","year":"1994","journal-title":"J. Exp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/bmb\/ldac034","article-title":"Management of complex regional pain syndrome in trauma and orthopaedic surgery: A systematic review","volume":"146","author":"Saed","year":"2023","journal-title":"Br. Med. Bull."},{"key":"ref_16","first-page":"102","article-title":"Lower extremity tendinopathies are associated with metabolic and chronic diseases: A systematic review","volume":"14","author":"Lagas","year":"2024","journal-title":"Muscles Ligaments Tendons J."}],"container-title":["Pathophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1873-149X\/33\/3\/71\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:56:28Z","timestamp":1790078188000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1873-149X\/33\/3\/71"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":16,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["pathophysiology33030071"],"URL":"https:\/\/doi.org\/10.3390\/pathophysiology33030071","relation":{},"ISSN":["1873-149X"],"issn-type":[{"value":"1873-149X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]}}}