{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:07:46Z","timestamp":1789103266711,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202378"],"award-info":[{"award-number":["82202378"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270098"],"award-info":[{"award-number":["82270098"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Sepsis remains a global health crisis with high mortality, due to a paucity of reliable diagnostic markers for accurate risk stratification and precision management. Interleukin\u201039 (IL\u201039), a novel immunomodulatory cytokine, plays an important role in regulating the pathophysiology of immunity, metabolism, and et\u00a0al. Here, we observed significantly elevated serum IL\u201039 levels in septic patients at admission compared with non\u2010sepsis ICU patients and healthy controls across two independent cohorts. Furthermore, circulating IL\u201039 concentrations could predict 28\u2010days survival in patients with sepsis. Single\u2010cell sequencing demonstrated that elevated IL\u201039 was derived from macrophages during sepsis. Meanwhile, supplementation of IL\u201039, via either recombinant protein (rmIL\u201039) administration or macrophage\u2010specific AAV\u2010mediated overexpression, profoundly aggravates multiple organ dysfunction and damage in septic mice. Consistently, macrophage IL\u201039 deficiency, via either macrophage\u2010conditional knockout or macrophage\u2010specific AAV\u2010mediated silence, protects against sepsis. Mechanistically, IL\u201039 engages GP130 to trigger MAPK\/P38 signaling, driving pro\u2010inflammatory cytokine production. Consequently, macrophage\u2010specific GP130 deletion abrogates IL\u201039\u2010induced sepsis aggravation. Finally, pharmaceutical inhibition of IL\u201039 with neutralizing antibodies can protect against sepsis. Together, these results highlight the dual clinical utility of IL\u201039, as both a robust biomarker with independent prognostic value for sepsis patient stratification and a promising therapeutic strategy for sepsis.<\/jats:p>","DOI":"10.1002\/advs.77663","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:33:55Z","timestamp":1789101235000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interleukin\u201039 is a Prognostic Biomarker and Therapy Target for Sepsis"],"prefix":"10.1002","author":[{"given":"Feng\u2010zhi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine Anhui Province Clinical Research Center for Critical Respiratory Medicine The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital)  Wuhu Anhui Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai\u2010jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine Anhui Province Clinical Research Center for Critical Respiratory Medicine The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital)  Wuhu Anhui Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5905-2790","authenticated-orcid":false,"given":"Yan","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine Anhui Province Clinical Research Center for Critical Respiratory Medicine The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital)  Wuhu Anhui Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010jie","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The Second Affiliated Hospital of Wannan Medical University  Wuhu Anhui Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Critical Care The Second Affiliated Hospital and Yuying Children's Hospital Key Laboratory of Pediatric Anesthesiology Ministry of Education Precision Anesthesiology Key Laboratory of Zhejiang Province Wenzhou Medical University  Wenzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010wu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Critical Care The Second Affiliated Hospital and Yuying Children's Hospital Key Laboratory of Pediatric Anesthesiology Ministry of Education Precision Anesthesiology Key Laboratory of Zhejiang Province Wenzhou Medical University  Wenzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4239-1786","authenticated-orcid":false,"given":"Yun\u2010long","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine Anhui Province Clinical Research Center for Critical Respiratory Medicine The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital)  Wuhu Anhui Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010hua","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine Anhui Province Clinical Research Center for Critical Respiratory Medicine The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital)  Wuhu Anhui Province People's Republic of 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