{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:43:14Z","timestamp":1790106194480,"version":"4.0.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic heart failure (HF) is a complex syndrome with significant morbidity and mortality, where inflammation is increasingly recognized as a critical factor in its progression. This study investigated the association of cytokine and chemokine profiles with mild cognitive impairment (MCI) and long-term mortality in patients with chronic HF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum concentrations of 13 cytokines were measured in 145 patients from the Cognition.Matters-HF study baseline cohort using a bead-based multiplex assay. Detailed clinical and cognitive evaluations were conducted, and survival data were tracked over 10 years. Cox proportional hazards regression and logistic regression models were applied to assess independent associations with mortality and MCI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No cytokine was independently associated with MCI. However, high interleukin-8 (IL-8) levels (&amp;gt;5.3\u2005pg\/ml) were significantly and independently associated with all-cause mortality (HR: 2.30; 95% CI: 1.30\u20134.07;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004). After adjusting for age and sex, IL-8 remained a strong predictor (Adj. HR: 2.28; 95% CI: 1.29\u20134.05;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.005). Further adjustments for clinical and biochemical variables showed that IL-8 (Adj. HR: 3.31; 95% CI: 1.61\u20136.79;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001) was the only cytokine independently associated with mortality. In the final multivariable model, IL-8 (Adj. HR: 2.57; 95% CI: 1.44\u20134.57;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001) remained a significant predictor along with age, body mass index, left atrial volume index, and six-minute walk distance. Other cytokines, including IL-6 and tumor necrosis factor-\u03b1, showed no independent associations with mortality.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest IL-8's unique role in HF pathophysiology and its potential as a biomarker and therapeutic target. Further research is needed to validate these results and explore the clinical utility of IL-8 modulation in HF management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2025.1677503","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T05:26:44Z","timestamp":1761283604000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["High interleukin-8 serum levels independently predict long-term all-cause mortality in chronic heart failure"],"prefix":"10.3389","volume":"12","author":[{"given":"Jan","family":"Traub","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Schuhmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Beyersdorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Frantz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"St\u00f6rk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Stoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Frey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1161\/CIRCRESAHA.123.323656","article-title":"The emerging field of cardioimmunology: past, present and foreseeable future","volume":"134","author":"Mann","year":"2024","journal-title":"Circ Res"},{"key":"B2","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/s41569-019-0315-x","article-title":"Reappraising the role of inflammation in heart failure","volume":"17","author":"Adamo","year":"2020","journal-title":"Nat Rev Cardiol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/s41569-020-00435-x","article-title":"Myocarditis and inflammatory cardiomyopathy: current evidence and future directions","volume":"18","author":"Tschope","year":"2021","journal-title":"Nat Rev Cardiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"831734","DOI":"10.3389\/fcvm.2021.831734","article-title":"Cognitive impairment in heart failure: landscape, challenges, and future directions","volume":"8","author":"Yang","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1111\/chf.12007","article-title":"Elevated levels of interleukin 6 and C-reactive protein associated with cognitive impairment in heart failure","volume":"19","author":"Athilingam","year":"2013","journal-title":"Congest Heart Fail"},{"key":"B6","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.jchf.2018.03.010","article-title":"Cognitive deficits and related brain lesions in patients with chronic heart failure","volume":"6","author":"Frey","year":"2018","journal-title":"JACC Heart Fail"},{"key":"B7","doi-asserted-by":"publisher","first-page":"6","DOI":"10.5334\/ojb.38","article-title":"Hospital-integrated biobanking as a service \u2013 the interdisciplinary bank of biomaterials and data Wuerzburg (ibdw)","volume":"5","author":"Geiger","year":"2018","journal-title":"Open J Bioresour"},{"key":"B8","volume-title":"TAP Test Battery of Attentional Performance. Version 2.2","author":"Zimmermann","year":"2009"},{"key":"B9","volume-title":"VVM2 Visual and Verbal Memory Test","author":"Schellig","year":"2009"},{"key":"B10","volume-title":"Wechsler Memory Scale\u2014Revised Manual","author":"Wechsler","year":"1987"},{"key":"B11","volume-title":"RWT Regensburger Wortfl\u00fcssigkeits-Test. Handanweisung","author":"Aschenbrenner","year":"2000"},{"key":"B12","first-page":"233","article-title":"Der HAMASCH 5 punkt test: erste normierungsergebnisse","volume":"13","author":"Haid","year":"2002","journal-title":"Z fur Neuropsychol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"30","DOI":"10.5551\/jat1994.8.30","article-title":"Changes in serum interleukin-8 and interleukin-12 levels in patients with ischemic heart disease in a Chinese population","volume":"8","author":"Zhou","year":"2001","journal-title":"J Atheroscler Thromb"},{"key":"B14","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1093\/eurjhf\/hft125","article-title":"Inflammatory cytokines in chronic heart failure: interleukin-8 is associated with adverse outcome. Results from CORONA","volume":"16","author":"Nymo","year":"2014","journal-title":"Eur J Heart Fail"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3203","DOI":"10.1002\/ehf2.14462","article-title":"Internal carotid artery blood flow and pulsatility index in cognitively impaired people with chronic heart failure","volume":"10","author":"Traub","year":"2023","journal-title":"ESC Heart Fail"},{"key":"B16","doi-asserted-by":"publisher","first-page":"291","DOI":"10.2174\/1573403X15666190313112841","article-title":"Heart failure and cognitive impairment: clinical relevance and therapeutic considerations","volume":"15","author":"Mene-Afejuku","year":"2019","journal-title":"Curr Cardiol Rev"},{"key":"B17","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1161\/01.CIR.93.4.704","article-title":"Tumor necrosis factor-alpha and tumor necrosis factor receptors in the failing human heart","volume":"93","author":"Torre-Amione","year":"1996","journal-title":"Circulation"},{"key":"B18","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/0014-5793(92)80909-Z","article-title":"Interleukin-8, a chemotactic and inflammatory cytokine","volume":"307","author":"Baggiolini","year":"1992","journal-title":"FEBS Lett"},{"key":"B19","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1007\/s10741-018-9716-x","article-title":"Role of cytokines and inflammation in heart function during health and disease","volume":"23","author":"Bartekova","year":"2018","journal-title":"Heart Fail Rev"},{"key":"B20","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s00011-004-1298-5","article-title":"Chemokines in the ischemic myocardium: from inflammation to fibrosis","volume":"53","author":"Frangogiannis","year":"2004","journal-title":"Inflamm Res"},{"key":"B21","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1038\/s41586-022-05060-x","article-title":"Spatial multi-omic map of human myocardial infarction","volume":"608","author":"Kuppe","year":"2022","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.jacc.2018.04.053","article-title":"Association of IL-8 with infarct size and clinical outcomes in patients with STEMI","volume":"72","author":"Shetelig","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"100037","DOI":"10.1016\/j.cytox.2020.100037","article-title":"An IL-6-IL-8 score derived from principal component analysis is predictive of adverse outcome in acute myocardial infarction","volume":"2","author":"Kristono","year":"2020","journal-title":"Cytokine X"},{"key":"B24","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1097\/01.mca.0000236288.94553.b4","article-title":"Role of interleukin-17 and interleukin-17-induced cytokines interleukin-6 and interleukin-8 in unstable coronary artery disease","volume":"17","author":"Hashmi","year":"2006","journal-title":"Coron Artery Dis"},{"key":"B25","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1161\/01.CIR.99.3.420","article-title":"Interleukin-8 mediates downregulation of tissue inhibitor of metalloproteinase-1 expression in cholesterol-loaded human macrophages: relevance to stability of atherosclerotic plaque","volume":"99","author":"Moreau","year":"1999","journal-title":"Circulation"},{"key":"B26","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/s41423-023-00974-6","article-title":"The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention","volume":"20","author":"Cambier","year":"2023","journal-title":"Cell Mol Immunol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/S0022-5223(98)70249-1","article-title":"Inhibition of interleukin-8 blocks myocardial ischemia-reperfusion injury","volume":"116","author":"Boyle","year":"1998","journal-title":"J Thorac Cardiovasc Surg"},{"key":"B28","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1186\/s40425-019-0706-x","article-title":"Phase I trial of HuMax-IL8 (BMS-986253), an anti-IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors","volume":"7","author":"Bilusic","year":"2019","journal-title":"J Immunother Cancer"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2025.1677503\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T05:26:46Z","timestamp":1761283606000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2025.1677503\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,24]]},"references-count":28,"alternative-id":["10.3389\/fcvm.2025.1677503"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2025.1677503","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,24]]},"article-number":"1677503"}}