{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:15:46Z","timestamp":1788358546201,"version":"build-2803163510"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ZonMw VIDI grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Inflammation in acute respiratory distress syndrome (ARDS) and COVID-19 causes disruption of the alveolar-capillary barrier and tissue damage, which has been associated with increased mortality. Elevated pro-inflammatory plasma biomarker (specifically IL-6) levels reflect the degree of systemic inflammation and are linked to severity of lung injury. Understanding the causal pathway between inflammation, interventions, and patient outcomes could improve clinical care.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess IL-6 as a mediator of effective interventions in ARDS and COVID-19.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We leveraged individual patient data from 5 large randomized controlled trials. Interventions were imatinib, anakinra, low tidal volume ventilation, high positive end\u2013expiratory pressure (PEEP), and simvastatin. We evaluated IL-6 as a mediator for the effectiveness of interventions on 28-day survival with joint modeling. Additionally, we analyzed the role of other pro-inflammatory markers (IL-8, tumor necrosis factor receptor 1, and C-reactive protein). The association between IL-6 and mortality was meta-analyzed using a random effects model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>For 2563 patients, IL-6 measures were available at baseline and at least 1 other timepoint. Interleukin-6 mediated the effects of imatinib, anakinra, and low tidal volume on mortality. Higher PEEP and simvastatin did not alter IL-6 trajectories. In all studies, there were associations between higher IL-6 concentrations and increased mortality over 28\u2009days (pooled hazard ratio [HR] for a log10-unit increase\u2009=\u20094.83, 95% CI, 3.50-6.66).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The mortality benefit by anakinra and imatinib in COVID-19 and low tidal volume ventilation in acute lung injury may operate through resolution of inflammation defined by a reduction in plasma IL-6 levels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajrccm\/aamag213","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T11:44:34Z","timestamp":1777031074000},"page":"1750-1760","source":"Crossref","is-referenced-by-count":2,"title":["Interleukin-6 is a mediator of therapeutic efficacy in acute lung injury"],"prefix":"10.1093","volume":"212","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7282-555X","authenticated-orcid":false,"given":"Lina","family":"Kramer","sequence":"first","affiliation":[{"name":"Intensive Care, Amsterdam UMC, The Amsterdam Institute for Infection and Immunity, University of Amsterdam , Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn S","family":"Calfee","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Departments of Medicine and Anesthesia, University of California, San Francisco , San Francisco, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F","family":"McAuley","sequence":"additional","affiliation":[{"name":"Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen\u2019s University Belfast , Belfast,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"O\u2019Kane","sequence":"additional","affiliation":[{"name":"Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen\u2019s University Belfast , Belfast,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurjan","family":"Aman","sequence":"additional","affiliation":[{"name":"Department of pulmonary medicine, Amsterdam UMC, Amsterdam Cardiovascular Sciences, VU University , Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Duijvelaar","sequence":"additional","affiliation":[{"name":"Department of pulmonary medicine, Amsterdam UMC, Amsterdam Cardiovascular Sciences, VU University , Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4713-3911","authenticated-orcid":false,"given":"Evangelos J","family":"Giamarellos-Bourboulis","sequence":"additional","affiliation":[{"name":"4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School , Athens,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Antonakos","sequence":"additional","affiliation":[{"name":"4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School , Athens,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn W","family":"Heymans","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Amsterdam UMC, Amsterdam Public Health Research Institute, VU University , Amsterdam,","place":["The 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