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Despite decades of extensive preclinical and clinical research, no disease-modifying pharmacological therapies have been established for ALI\/ARDS, with all-cause mortality remaining persistently between 40% and 60%. The onset and progression of ALI\/ARDS are universally accompanied by robust release of the endogenous catecholamines epinephrine (EPI) and norepinephrine (NE), which signal via adrenergic receptors (ARs) expressed on nearly all structural and immune cell populations in the lung. ARs are G protein-coupled receptors (GPCRs) that serve as the core molecular interface between the sympathetic nervous system (SNS) and pulmonary innate immunity, modulating inflammatory responses, barrier integrity, and pathogen clearance within the lung. Recent seminal studies have delineated central neural circuits governing lung inflammation via sympathetic\u2013adrenergic signaling, defined cell subset-specific bidirectional functions of ARs activation, and yielded critical mechanistic insights into the longstanding adrenergic paradox, substantially advancing our neuroimmunological understanding of ALI\/ARDS pathogenesis. In this review, we systematically delineate the cell-type-specific and disease context-dependent roles of ARs subtypes in regulating pulmonary innate immune responses in both direct (pneumonia-induced) and indirect (sepsis-induced) ALI\/ARDS. We critically integrate the canonical and non-canonical signaling pathways of ARs, and address the longstanding \u201cadrenergic paradox\u201d\u2014the context-dependent bidirectional effects of ARs signaling, which can both suppress excessive inflammation and impair host antibacterial defense. We further examine the translational challenges of ARs-targeted therapies, including the failure of prior clinical trials, and provide a mechanistic framework for the development of optimized therapeutic strategies for ALI\/ARDS.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1744464","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:23:45Z","timestamp":1783571025000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Adrenergic receptors: a key determinant of outcomes in bacterial pneumonia and bacterial sepsis-associated acute lung injury\/acute respiratory distress syndrome through participation in pulmonary innate immune response"],"prefix":"10.3389","volume":"17","author":[{"given":"Lin","family":"Zeng","sequence":"first","affiliation":[{"name":"LiShizhen College of Traditional Chinese Medicine, Huanggang Normal University","place":["Huanggang, Hubei, China"]},{"name":"Hubei Key Laboratory of Germplasm Improvement and Utilization of Dabie Shan Dao-di Herbs (Huanggang Normal University)","place":["Huanggang, Hubei, China"]},{"name":"LiShizhen Culture and Industry Research Center of Traditional Chinese Medicine","place":["Huanggang, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinshu","family":"Yang","sequence":"additional","affiliation":[{"name":"LiShizhen College of Traditional Chinese Medicine, Huanggang Normal University","place":["Huanggang, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangtian","family":"Yan","sequence":"additional","affiliation":[{"name":"LiShizhen College of Traditional Chinese Medicine, Huanggang Normal University","place":["Huanggang, Hubei, China"]},{"name":"Hubei Key Laboratory of Germplasm Improvement and Utilization of Dabie Shan Dao-di Herbs (Huanggang Normal University)","place":["Huanggang, Hubei, China"]},{"name":"LiShizhen Culture and Industry Research Center of Traditional Chinese Medicine","place":["Huanggang, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.5669","article-title":"Acute respiratory distress syndrome: the Berlin definition","volume":"307","author":"Ards Dtf","year":"2012","journal-title":"Jama"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(67)90168-7","article-title":"Acute respiratory distress in adults","volume":"2","author":"Ashbaugh","year":"1967","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.149.3.7509706","article-title":"The American-European Consensus Conference on ARDS. 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