{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T12:28:29Z","timestamp":1787228909248,"version":"build-2736575974"},"reference-count":159,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"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>Severe pneumonia is a common critical illness encountered in clinical practice. Although mechanical ventilation is essential for life support, it can paradoxically result in ventilator-induced lung injury and exacerbate pulmonary inflammation. Interleukin-6 (IL-6) is a key pleiotropic cytokine with both proinflammatory and immunometabolic effects, playing a crucial role in regulating the alveolar microenvironment and systemic immune responses in patients with severe pneumonia. Current evidence suggests that IL-6 overexpression is closely associated with increased alveolar inflammation, immune dysregulation, and damage to lung parenchyma. Nevertheless, the dynamic changes of IL-6 during mechanical ventilation and their clinical implications have yet to be fully clarified. This review comprehensive narrative reviewexplores the biological properties of IL-6, its production and regulatory mechanisms during alveolar inflammation in severe pneumonia, the effects of mechanical ventilation on IL-6 levels, IL-6-mediated immune dysregulation and lung injury, its diagnostic and prognostic value as a biomarker, targeted therapeutic strategies against IL-6, and future research directions. By synthesizing recent basic and clinical evidence, this comprehensive narrative review seeks to establish a theoretical foundation for precision medicine and advance the development of individualized immunomodulatory strategies for this patient population.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1915511","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:56:51Z","timestamp":1787227011000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms and clinical research progress of IL-6-mediated crosstalk between the alveolar microenvironment and the immune system in patients with severe pneumonia undergoing mechanical ventilation"],"prefix":"10.3389","volume":"17","author":[{"given":"Jianxiong","family":"Xiao","sequence":"first","affiliation":[{"name":"Intensive Care Unit, Wanbei Coal Electric Group General Hospital","place":["Suzhou, Anhui, 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