{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T06:33:35Z","timestamp":1767335615157,"version":"3.48.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002977","name":"Dalhousie University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007670","name":"Dalhousie Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007670","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020170","name":"Research Nova Scotia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020170","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002330","name":"Nova Scotia Department of Health and Wellness","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sternotomy provides access to the mediastinum, heart and great vessels for congenital cardiac surgery in children. The contribution of this incision to the systemic inflammatory response during open-heart surgery, particularly in combination with the complement-mediated response to cardiopulmonary bypass (CPB), is unknown. This study aimed to characterize the inflammatory mediator profile of sternotomy and contrast that with CPB-associated inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study is a\n                      <jats:italic>post-hoc<\/jats:italic>\n                      analysis of a single-arm prospective clinical study (NCT05154864) of 40 pediatric patients undergoing congenital cardiac surgery with CPB. Arterial blood samples were taken before and after sternotomy, but before CPB initiation (sternotomy phase), and after CPB exposure (CPB phase). Thirty-three inflammatory mediators from the cytokine, chemokine, complement, and adhesion molecule families were measured. The mediator changes were calculated for each phase and described using median fold changes. A principal component analysis with hierarchical clustering (PCA-HCPC) was conducted on mediator changes over the sternotomy phase.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared to baseline, all 16 cytokines and chemokines assessed increased through the sternotomy phase, while complement and adhesion molecules were static or decreased. The most active mediators were IL-1\u03b2 (3.3x median fold increase), CXCL2 (3.3x), IL-6 (2.6x), IL-10 (2.6x), GM-CSF (2.3x), IL-1\u03b1 (2.2x) and IL-2 (1.7x). The PCA-HCPC showed three statistically significant clusters, cluster 1 grouped cytokines and chemokines with the sternotomy phase, while complement mediators and adhesion molecules were in separate clusters. In contrast to the CPB exposure, sternotomy showed a predominant contribution of TNF, IL-1\u03b1, IL-1\u03b2, IL-2, TRAIL, CCL3, CCL4, CXCL1, CXCL2 and GM-CSF to the systemic inflammatory response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Sternotomy and related tissue trauma produce a distinct systemic inflammatory mediator profile, consisting of pro-inflammatory cytokines and chemokines but not complement. The mediators IL-6, CXCL8, IL-1Ra and IL-10 are sequentially induced by both sternotomy and CPB, representing sequential immunologic stimulation during the cardiac operation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1617524","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T06:28:56Z","timestamp":1767335336000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The distinct contribution of sternotomy to the systemic inflammatory response during children's heart surgery"],"prefix":"10.3389","volume":"16","author":[{"given":"Joel David","family":"Bierer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Paffile","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger","family":"Stanzel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Henderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Sapp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pantelis","family":"Andreou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean Sylvia","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Horne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/PCC.0000000000000759","article-title":"Cardiopulmonary bypass-induced inflammatory response: Pathophysiology and treatment","volume":"17","author":"Bronicki","year":"2016","journal-title":"Pediatr Crit Care Med"},{"key":"B2","article-title":"The systemic inflammatory response to cardiac surgery implications for the anesthesiologist","volume":"1","author":"Warltier","year":"2002","journal-title":"Anesthesiology."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212667","article-title":"Methylprednisolone for heart surgery in infants \u2014 A randomized, controlled trial","volume":"387","author":"Hill","year":"2022","journal-title":"New Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1001\/jama.2022.9376","article-title":"Effect of nitric oxide via cardiopulmonary bypass on ventilator-free days in young children undergoing congenital heart disease surgery: the NITRIC randomized clinical trial","volume":"328","author":"Schlapbach","year":"2022","journal-title":"J Am Med Assoc"},{"key":"B5","doi-asserted-by":"crossref","DOI":"10.1080\/08941939.2020.1726531","article-title":"Retrospective comparison of endoscopic versus open procedure for mitral valve disease","volume":"34","author":"Jiang","year":"2021","journal-title":"J Invest Surgery."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/icvts\/ivu343","article-title":"Routine thymectomy in congenital cardiac surgery changes adaptive immunity without clinical relevance","volume":"20","author":"Roosen","year":"2015","journal-title":"Interact Cardiovasc Thorac Surg"},{"key":"B7","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1111\/j.1524-475X.2008.00410.x","article-title":"Growth factors and cytokines in wound healing","volume":"16","author":"Barrientos","year":"2008","journal-title":"Wound Repair Regeneration."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms19103217","article-title":"The role of chemokines in wound healing","volume":"3217","author":"Ridiandries","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B9","doi-asserted-by":"crossref","first-page":"760","DOI":"10.4103\/ija.IJA_379_17","article-title":"Basics of cardiopulmonary bypass","volume":"61","author":"Sarkar","year":"2017","journal-title":"Indian J Anaesth."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1177\/2150135119870176","article-title":"Ultrafiltration in pediatric cardiac surgery review","volume":"10","author":"Bierer","year":"2019","journal-title":"World J Pediatr Congenit Heart Surg"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40001-024-02156-0","article-title":"Unmasking culprits: novel analysis identifies complement factors as potential therapeutic targets to mitigate inflammation during children's heart surgery","volume":"29","author":"Bierer","year":"2024","journal-title":"Eur J Med Res"},{"key":"B12","first-page":"95","article-title":"Humoral immune response during coronary artery bypass grafting : A comparison of limited approach, \"Off-pump\" Technique, and conventional cardiopulmonary bypass","volume":"102","author":"Diegeler","year":"2000","journal-title":"Circulation."},{"key":"B13","doi-asserted-by":"crossref","DOI":"10.1378\/chest.116.4.892","article-title":"Complement activation in coronary artery bypass grafting patients without cardiopulmonary bypass: the role of tissue injury by surgical incision","volume":"116","author":"Gu","year":"1999","journal-title":"Chest."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.21470\/1678-9741-2020-0158","article-title":"Comparison between different tricuspid valve procedures through postoperative inflammation and myocardial enzymes","volume":"36","author":"Sun","year":"2021","journal-title":"Braz J Cardiovasc Surg"},{"key":"B15","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1214\/ss\/1032280214","article-title":"Bootstrap confidence intervals","volume":"11","author":"Diciccio","year":"1996","journal-title":"Stat Science."},{"key":"B16","article-title":"FactoMineR: an R package for multivariate analysis","volume":"25","author":"L\u00ea","year":"2008","journal-title":"JSS J Stat Software"},{"key":"B17","first-page":"1","article-title":"Principal component methods-hierarchical clustering-partitional clustering: why would we need to choose for visualizing data","volume-title":"Technical report - agrocampus","author":"Husson","year":"2010"},{"key":"B18","doi-asserted-by":"crossref","DOI":"10.1016\/j.chemolab.2011.08.009","article-title":"Quantification and statistical significance analysis of group separation in NMR-based metabonomics studies","volume":"109","author":"Goodpaster","year":"2011","journal-title":"Chemometrics Intelligent Lab Systems."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-025-11157-w","article-title":"Complement activation by the artificial surface of cardiopulmonary bypass is a persistent clinical problem","volume":"15","author":"Bierer","year":"2025","journal-title":"Sci Rep"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2004.02.007","article-title":"A new role in hemostasis for the adhesion receptor P-selectin","volume":"10","author":"Cambien","year":"2004","journal-title":"Trends Mol Med"},{"key":"B21","article-title":"Leukocyte\u2013endothelial cell adhesion","volume-title":"Inflammation and the microcirculation","author":"Granger","year":"2010"},{"key":"B22","doi-asserted-by":"crossref","DOI":"10.1007\/s00011-013-0633-0","article-title":"TNF- a signalling and inflammation : interactions between old acquaintances","volume":"62","author":"Zelova","year":"2013","journal-title":"Inflammation Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1510\/icvts.2005.125880","article-title":"First experience with closed circuit\/centrifugal pump extracorporeal circulation: cellular trauma, coagulatory, and inflammatory response","volume":"5","author":"Just","year":"2006","journal-title":"Interact Cardiovasc Thorac Surg"},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejcts.2005.12.028","article-title":"Relation of inflammatory cytokines to atrial fibrillation after off-pump coronary artery bypass grafting","volume":"29","author":"Ishida","year":"2006","journal-title":"Eur J Cardio-Thoracic Surgery."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.931523","article-title":"Leptin and leptin soluble receptor changes after pulmonary endarterectomy: relations to cortisol and cytokine network","volume":"58","author":"Maruna","year":"2009","journal-title":"Physiol Res"},{"key":"B26","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.ejcts.2010.05.018","article-title":"Predictors of infection after pulmonary endarterectomy for chronic thrombo-embolic pulmonary hypertension","volume":"39","author":"Maruna","year":"2011","journal-title":"Eur J Cardio-Thoracic Surgery."},{"key":"B27","article-title":"Circulating endothelin in patients undergoing coronary artery bypass grafting","volume":"9","author":"Mathies","year":"1995","journal-title":"Eur J Cardio-Thoracic Surgery."},{"key":"B28","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3390\/cells11030359","article-title":"Interconnections between inflammageing and immunosenescence during ageing","volume":"11","author":"Teissier","year":"2022","journal-title":"Cells."},{"key":"B29","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2010-07-273417","article-title":"Interleukin-1 in the pathogenesis and treatment of inflammatory diseases","volume":"117","author":"Dinarello","year":"2011","journal-title":"Blood."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s00068-023-02388-5","article-title":"Traumatic inflammatory response: pathophysiological role and clinical value of cytokines","author":"Li","year":"2024","journal-title":"Eur J Trauma Emergency Surgery."},{"key":"B31","doi-asserted-by":"publisher","first-page":"3217","DOI":"10.3390\/ijms19103217","article-title":"The role of chemokines in wound healing","volume":"19","author":"Ridiandries","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.2147\/ITT.S262566","article-title":"GM-CSF: A promising target in inflammation and autoimmunity","volume":"9","author":"Lee","year":"2020","journal-title":"Immunotargets Ther"},{"key":"B33","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1177\/0885066610384188","article-title":"Interleukin-6 in surgery, trauma, and critical care part II: clinical implications","volume":"26","author":"Jawa","year":"2011","journal-title":"J Intensive Care Med"},{"key":"B34","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1186\/ar1917","article-title":"Interleukin-6 and chronic inflammation","volume":"8","author":"Gabay","year":"2006","journal-title":"Arthritis Res Ther"},{"key":"B35","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1001\/archsurg.135.3.291","article-title":"Is interleukin 6 an early marker of injury severity following major trauma in humans","volume":"135","author":"Gebhard","year":"2000","journal-title":"Arch Surg"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3109\/08830189809043005","article-title":"Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist","volume":"16","author":"Dinarello","year":"1998","journal-title":"Int Rev Immunol"},{"key":"B37","doi-asserted-by":"crossref","DOI":"10.1089\/wound.2013.0461","article-title":"Regenerative wound healing: the role of interleukin-10","volume":"3","author":"King","year":"2014","journal-title":"Adv Wound Care (New Rochelle)."},{"key":"B38","article-title":"NF-\u03baB signalling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct Target Ther"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-018-1164-5","article-title":"An overview of mast cell pattern recognition receptors","volume":"67","author":"Agier","year":"2018","journal-title":"Inflammation Res"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.04.045","article-title":"Mast cells in innate immunity","volume":"114","author":"Marshall","year":"2004","journal-title":"J Allergy Clin Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042617-053352","article-title":"Signalling and function of interleukin-2 in T lymphocytes","volume":"36","author":"Ross","year":"2018","journal-title":"Annu Rev Immunol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.immuni.2013.01.004","article-title":"Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy","author":"Liao","year":"2013","journal-title":"Vol. 38 Immunity."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1177\/1535370216675773","article-title":"The contribution of interleukin-2 to effective wound healing","volume":"242","author":"Doersch","year":"2017","journal-title":"Exp Biol Med"},{"key":"B44","first-page":"76","article-title":"Role of interleukin-2 in wound healing: A review study","volume":"3","author":"Handayani","year":"2023","journal-title":"Trends Infection Global Health"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12967-023-04255-8","article-title":"Novel inflammatory mediator profile observed during pediatric heart surgery with cardiopulmonary bypass and continuous ultrafiltration","volume":"21","author":"Bierer","year":"2023","journal-title":"J Transl Med"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/02676591251374252","article-title":"The immunomodulatory effect of continuous ultrafiltration during pediatric cardiac surgery","author":"Bierer","year":"2025","journal-title":"Perfusion."}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1617524\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T06:29:00Z","timestamp":1767335340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1617524\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,2]]},"references-count":46,"alternative-id":["10.3389\/fimmu.2025.1617524"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1617524","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,2]]},"article-number":"1617524"}}