{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:48:28Z","timestamp":1787500108972,"version":"build-2736575974"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"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:p>\n                    Severe pneumonia is an acute lung parenchyma infectious disease with a high incidence and mortality. The role of interleukin-40 (IL-40) in estimating mortality in patients with severe pneumonia remains unknown. This study aims to reveal the clinical application of IL-40 at intensive care unit (ICU) admission as a potentially novel biomarker to predict the mortality risk of severe pneumonia. Patients with severe pneumonia (\n                    <jats:italic>n<\/jats:italic>\n                    = 104), patients with non-severe pneumonia (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a050), and healthy controls (\n                    <jats:italic>n<\/jats:italic>\n                    = 86) from May 2023 to May 2025 were enrolled. The serum IL-40 levels were measured at admission, and the 28-day survival status of the participants was compared. Furthermore, the area under the receiver operating characteristic curve (AUC) of IL-40 at ICU admission for 28-day survival was used to evaluate the ability of IL-40 in predicting the mortality of severe pneumonia. Kaplan\u2013Meier survival curves were analyzed to evaluate the relationship between IL-40 and the mortality risk of severe pneumonia. IL-40 levels at ICU admission in patients with severe pneumonia were significantly higher than those in patients with non-severe pneumonia and healthy controls. IL-40 levels in non-survivors were significantly higher than those in survivors. The AUC of IL-40 for predicting the mortality risk of severe pneumonia was highest among the indicators. IL-40 and Sequential Organ Failure Assessment (SOFA) scores at ICU admission of patients with severe pneumonia were found to be independent predictors of 28-day mortality. The AUC of IL-40 combined with SOFA score for estimating 28-day mortality in patients with severe pneumonia increased from 0.7626 to 0.7980. Moreover, patients with severe pneumonia with higher IL-40 levels (\u22651.244 ng\/mL) had poorer survival than those with lower levels (&amp;lt;1.244 ng\/mL) (\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.001). The IL-40 at ICU admission was valuable for predicting the mortality risk of severe pneumonia. These findings can be used as an early biomarker for early clinical decision-making in treating patients with severe pneumonia.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1804357","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T20:10:22Z","timestamp":1779912622000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Interleukin-40 as a biomarker of mortality risk in patients with severe pneumonia"],"prefix":"10.3389","volume":"17","author":[{"given":"Hong","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Blood Transfusion, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanyi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoliang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/ccm.0000000000005498","article-title":"Etiology, treatments, and outcomes of patients with severe community-acquired pneumonia in a large U.S. sample","volume":"50","author":"Haessler","year":"2022","journal-title":"Crit Care Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0b013e32835f27be","article-title":"Hospital-acquired pneumonia and ventilator-associated pneumonia: Recent advances in epidemiology and management","volume":"19","author":"Barbier","year":"2013","journal-title":"Curr Opin Pulm Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1016\/s1473-3099(24)00176-2","article-title":"Global, regional, and national incidence and mortality burden of non-covid-19 lower respiratory infections and aetiologies, 1990-2021: A systematic analysis from the Global Burden of Disease Study 2021","volume":"24","year":"2024","journal-title":"Lancet Infect Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2021-065871","article-title":"Management of pneumonia in critically ill patients","volume":"375","author":"Cill\u00f3niz","year":"2021","journal-title":"Bmj"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.4084\/mjhid.2023.057","article-title":"Diagnosis and prognosis evaluation of severe pneumonia by lung ultrasound score combined with serum inflammatory markers","volume":"15","author":"Fu","year":"2023","journal-title":"Mediterr J Hematol Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201908-1581ST","article-title":"Diagnosis and treatment of adults with community-acquired pneumonia. 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