{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:41:24Z","timestamp":1792672884051,"version":"4.5.0"},"reference-count":100,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:00:00Z","timestamp":1792195200000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Interleukin\u20106 (IL\u20106) is frequently measured in heart failure with reduced ejection fraction (HFrEF), but its clinical utility remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess IL\u20106 as a biomarker in HFrEF, with emphasis on the effect of treatments (pharmacodynamics) and translation readiness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MEDLINE and EMBASE were searched through June 2026. Using AI\u2010assisted full\u2010text screening with manual adjudication, eligible studies were classified using BEST classification as prognostic, predictive and\/or pharmacodynamic biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eighty studies met inclusion criteria (59 pharmacodynamic, 21 prognostic, 3 predictive; categories overlapping). Across prognostic studies, higher IL\u20106 consistently tracked disease severity and cardiovascular mortality risk, but associations with hospitalization and composite endpoints weakened after adjustment for natriuretic peptides, limiting incremental clinical value. Pharmacodynamic studies showed that several interventions reduce circulating IL\u20106\u2014most consistently statins and levosimendan\u2014while findings were heterogeneous for exercise, cardiac device, and sodium\u2013glucose co\u2010transporter\u20102 inhibitors. However, IL\u20106 changes did not consistently parallel clinical benefit, arguing against its use as a surrogate measure for outcome improvement. No study supported IL\u20106 as a predictive biomarker. Assay heterogeneity was substantial, with limited use of in\u00a0vitro diagnosis\u2010grade assays, representing a major barrier to qualification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In HFrEF, IL\u20106 reflects inflammatory burden and may serve as pharmacodynamic readout in mechanistic studies, but it is not supported for treatment selection and adds limited prognostic information beyond natriuretic peptides. Progress towards translational utility requires standardized measurements and, potentially, biomarkers reflecting the IL\u20106 axis beyond IL\u20106 alone.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/eci.70261","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T09:30:48Z","timestamp":1792229448000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Why Circulating Interleukin\u20106 Is Not Yet a Standalone Clinically Actionable Biomarker in\n                    <scp>HFrEF<\/scp>\n                    : A Context\u2010of\u2010Use Review"],"prefix":"10.1111","volume":"56","author":[{"given":"Yongxin","family":"Ye","sequence":"first","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg 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