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TREM-1 activation leads to the production and release of proinflammatory cytokines, chemokines, as well as its own expression and circulating levels of the cleaved soluble extracellular portion of TREM-1 (sTREM-1). Because patients with sepsis and septic shock show elevated sTREM-1 levels, TREM-1 has attracted attention as an important contributor to the inadequate immune response in this often-deadly condition. Since 2001, when the first blockade of TREM-1 in sepsis was performed, many potential TREM-1 inhibitors have been established in animal models. However, only one of them, nangibotide, has entered clinical trials, which have yielded promising data for future treatment of sepsis, septic shock, and other inflammatory disease such as COVID-19. This review discusses the TREM-1 pathway and important ligands, and highlights the development of novel inhibitors as well as their clinical potential for targeted treatment of various inflammatory conditions.<\/jats:p>","DOI":"10.1186\/s13054-024-04798-2","type":"journal-article","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T21:01:52Z","timestamp":1704747712000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Triggering receptor expressed on myeloid cells-1 in sepsis, and current insights into clinical studies"],"prefix":"10.1186","volume":"28","author":[{"given":"Vivienne","family":"Theobald","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix Carl Fabian","family":"Schmitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara Simone","family":"Middel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Gaissmaier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus Alexander","family":"Weigand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,9]]},"reference":[{"issue":"10","key":"4798_CR1","doi-asserted-by":"publisher","first-page":"4991","DOI":"10.4049\/jimmunol.164.10.4991","volume":"164","author":"A Bouchon","year":"2000","unstructured":"Bouchon A, Dietrich J, Colonna M. 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MW received grants from K\u00f6hler Chemie, DFG and BMBF, consulting fees from B. Braun, Gilead, Mundipharma and Boehringer Ingelheim, and payment or honoraria for lectures, presentations, or educational events from MSD, Gilead, Shionogi, Pfizer and Beckman Coulter. Dr Weigand is also a patent owner (EP17185036.5 and EP17198330.7), has participated on advisory boards for MSD, Gilead, Shionogi, Biotest, Pfizer, Eumedica, SOBI and Beckman Coulter, is the vice-head of the German Sepsis Society and member of the scientific advisory council of PEG, and is cofounder of Delta Theragnostics. TB received scientific grants from Deutsche Forschungsgemeinschaft (DFG), Innovation Fund of the Federal Joint Committee (G-BA), Dietmar Hopp Stiftung, Heidelberg Foundation of Surgery as well as Stiftung Universit\u00e4tsmedizin Essen. Moreover, he received honoraria for lectures as well as advisory board participation from Baxter Deutschland GmbH, Sch\u00f6chl medical education GmbH, Boehringer Ingelheim Pharma GmbH, CSL Behring GmbH, Astellas Pharma GmbH, B. Braun Melsungen AG, MSD Sharp & Dohme GmbH, BRAHMS GmbH, L\u00fccke Kongresse GmbH, Georg Thieme Verlag GmbH as well as Akademie f\u00fcr Infektionsmedizin e.V.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17"}}