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Acute ethanol intoxication (EI) induces complex local and systemic anti-inflammatory effects and influences the early outcomes of traumatized patients. Here, we evaluated its effects on the BI-induced expression of local inflammatory mediators in the trauma-remote organs the lungs and liver. Male mice were exposed to ethanol as a single oral dose (5g\u00b7kg\u20131, 32%) before inducing a moderate blunt TBI. Sham groups underwent the same procedures without TBI. Ether 3 or 6h after the TBI, the lung and liver were collected. The gene expression of HMGB1, IL-6, MMP9, IL-1\u03b2, and TNF as well as the homogenate protein levels of receptor for advanced glycation end products (RAGE), IL-6, IL-1\u03b2, and IL-10 were analyzed. Liver samples were immunohistologically stained for HMGB1. EI decreased the gene expressions of the proinflammatory markers HMGB1, IL-6, and MMP9 in the liver upon TBI. In line with the reduced gene expression, the TBI-induced protein expression of IL-6 in liver tissue homogenates was significantly reduced by EI at 3h after TBI. While the histological HMGB1 expression was enhanced by TBI, the RAGE protein expression in the liver tissue homogenates was diminished after TBI. EI reduced the histological HMGB1 expression and enhanced the hepatic RAGE protein expression at 6h post TBI. With regard to the lungs, EI significantly reduced the gene expressions of HMGB1, IL-6, IL-1\u03b2, and TNF upon TBI, without significantly affecting the protein expression levels of inflammatory markers (RAGE, IL-6, IL-1\u03b2, and IL-10). At the early stage of TBI-induced inflammation, the gene expression of inflammatory mediators in both the lungs and liver is susceptible to ethanol-induced remote effects. Taken together, EI may alleviate the TBI-induced pro-inflammatory response in the trauma-distant organs, the lungs and liver, via the HMGB1-RAGE axis.<\/jats:p>","DOI":"10.3390\/ijms21218181","type":"journal-article","created":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T21:39:56Z","timestamp":1604180396000},"page":"8181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Ethanol Intoxication Alleviates the Inflammatory Response of Remote Organs to Experimental Traumatic Brain Injury"],"prefix":"10.3390","volume":"21","author":[{"given":"Baolin","family":"Xu","sequence":"first","affiliation":[{"name":"Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto von Guericke University, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akila","family":"Chandrasekar","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"olde Heuvel","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maciej","family":"Powerski","sequence":"additional","affiliation":[{"name":"Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto von Guericke University, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksander","family":"Nowak","sequence":"additional","affiliation":[{"name":"Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto von Guericke University, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9496-9909","authenticated-orcid":false,"given":"Laurens","family":"Noack","sequence":"additional","affiliation":[{"name":"Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto von Guericke University, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jazan","family":"Omari","sequence":"additional","affiliation":[{"name":"Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto von Guericke University, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Huber-Lang","sequence":"additional","affiliation":[{"name":"Institute of Clinical and Experimental Trauma-Immunology, University Hospital Ulm, Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9935-6899","authenticated-orcid":false,"given":"Francesco","family":"Roselli","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE)-Ulm, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Borna","family":"Relja","sequence":"additional","affiliation":[{"name":"Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto von Guericke University, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S193","DOI":"10.1038\/nature16035","article-title":"Global neurotrauma research challenges and opportunities","volume":"527","author":"Rubiano","year":"2015","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2147\/CEOR.S44625","article-title":"The costs of traumatic brain injury: A literature review","volume":"5","author":"Humphreys","year":"2013","journal-title":"Clin. 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