{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:21Z","timestamp":1787026581130,"version":"build-2736575974"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Sepsis arises from a dysregulated host inflammatory response to infection. The levels and pathogenic role of interleukin-37 (IL-37) in pediatric sepsis remain to be fully elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum IL-37 concentrations were measured in two independent cohorts of pediatric patients with sepsis from Chongqing (discovery cohort, n=40) and Sichuan (validation cohort, n=105). The immunomodulatory effects of IL-37 were systematically investigated through: 1) a murine sepsis model (cecal ligation and puncture), and 2) ex vivo experiments using peripheral blood mononuclear cells (PBMCs) from patients under standardized culture conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Admission serum IL-37 levels were significantly higher in pediatric patients with sepsis compared to non-septic patients and healthy controls. To assess its diagnostic potential, ROC curve analyses were performed, yielding areas under the curve (AUC) of 0.76 [P&amp;lt;0.0001; 95% confidence interval (95% CI), 0.66 - 0.85] and 0.77 [P&amp;lt;0.0001; 95% CI, 0.71 - 0.84] from the two medical centers. In septic mice, therapeutic administration of recombinant IL-37 significantly attenuated systemic inflammation (reduced IL-6, CXCL-1, CCL-2; increased IL-10), decreased the proportion of M1 macrophages without altering total macrophage counts in peritoneal lavage fluids (PLF), and improved survival rates.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , IL-37 neutralization with a specific antibody in septic PBMCs increased the percentages of CD4+ T cells and NKT cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies elevated IL-37 as a potential diagnostic biomarker for pediatric sepsis and demonstrates its role in modulating hyperinflammation and immune cell differentiation. IL-37 represents a promising therapeutic target for pediatric sepsis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1765956","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:19:16Z","timestamp":1770898756000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The diagnostic and immunomodulatory role of IL-37 in pediatric sepsis"],"prefix":"10.3389","volume":"17","author":[{"given":"Jin","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changrui","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Children\u2019s Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiqi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.45","article-title":"Sepsis and septic shock","author":"Hotchkiss","year":"2016","journal-title":"Nat 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