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Excessive monocyte influx into the alveolar space can exacerbate lung damage, worsening patient outcomes. Delaying or reducing monocyte recruitment into the alveoli space after the injury has been proposed as a strategy to balance the inflammatory response and mitigate lung damage. In the present study, we assessed the possible role of the CCL2-CCR2 axis as a therapy for controlling acute lung injury after the initial neutrophil-driven influx. We administered a CCL2-antibody (CCL2-Ab) or a CCR2-antagonist (CCR2-Ant) locally into the lung following lung injury induced by HCl\/LPS instillation. Our results show that after 24\u00a0h, both treatments transiently reduced monocyte infiltration into the bronchoalveolar space. After 72\u00a0h, neither CCL2-Ab nor CCR2-Ant sustained a reduced monocyte infiltration or significantly alleviated alveolar or lung inflammation. CCR2-Ant prevented an increase of alveolar permeability, but neither of both treatments, CCL2-Ab nor CCR2-Ant, improved lung damage or function. Our findings indicate that blocking the CCL2-CCR2 axis to control monocyte trafficking at early stages of lung injury is insufficient to control inflammation or prevent disease progression. These results highlight the complexity of ARDS pathophysiology and suggest that alternative strategies may be required to effectively modulate monocyte-driven lung inflammation.<\/jats:p>","DOI":"10.1038\/s41598-025-11971-2","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T08:24:55Z","timestamp":1756196695000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacological inhibition of the CCL2-CCR2 axis fails to reduce inflammation in a rat model of acute lung injury"],"prefix":"10.1038","volume":"15","author":[{"given":"Marta","family":"Camprub\u00ed-Rimblas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neus","family":"Tantiny\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Artigas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Guillamat-Prats","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"11971_CR1","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1056\/NEJM200005043421806","volume":"342","author":"LB Ware","year":"2000","unstructured":"Ware, L. 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