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Ethanol exacerbates pulmonary complications after burn injury in mice, regardless of frequency of ethanol exposures
Burn injuries are associated with significant morbidity and mortality, and lungs are the most common organ to fail. Interestingly, patients with alcohol intoxication at the time of burn have worse clinical outcomes, including pulmonary complications. Using a clinically relevant murine model, we have...
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| Published in: | Burns 2023-12, Vol.49 (8), p.1935-1943 |
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| container_end_page | 1943 |
| container_issue | 8 |
| container_start_page | 1935 |
| container_title | Burns |
| container_volume | 49 |
| creator | Khair, Shanawaj Walrath, Travis M Curtis, Brenda J Orlicky, David J McMahan, Rachel H Kovacs, Elizabeth J |
| description | Burn injuries are associated with significant morbidity and mortality, and lungs are the most common organ to fail. Interestingly, patients with alcohol intoxication at the time of burn have worse clinical outcomes, including pulmonary complications. Using a clinically relevant murine model, we have previously reported that episodic ethanol exposure before burn exacerbated lung inflammation. Specifically, intoxicated burned mice had worsened pulmonary responses, including increased leukocyte infiltration and heightened levels of CXCL1 and IL-6. Herein, we examined whether a single binge ethanol exposure before scald burn injury yields similar pulmonary responses. C57BL/6 male mice were given ethanol (1.2g/kg) 30min before a 15% total body surface area burn. These mice were compared to a second cohort given episodic ethanol binge for a total of 6 days (3 days ethanol, 4 days rest, 3 days ethanol) prior to burn injury. 24hours after burn, histopathological examination of lungs were performed. In addition, survival, and levels of infiltrating leukocytes, CXCL1, and IL-6 were quantified. Episodic and single ethanol exposure before burn decreased survival compared to burn only mice and sham vehicle mice, respectively (p |
| doi_str_mv | 10.1016/j.burns.2023.07.008 |
| format | article |
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•Alcohol exposure prior to burn injury worsens clinical outcomes.•Single and episodic ethanol binge before burn similarly worsen lung inflammation.•Both ethanol exposure regimens increase lung CXCL1 and IL-6 after burn.•Ethanol presence at the time of burn is more relevant than longer ethanol exposure.</description><identifier>ISSN: 0305-4179</identifier><identifier>ISSN: 1879-1409</identifier><identifier>EISSN: 1879-1409</identifier><identifier>DOI: 10.1016/j.burns.2023.07.008</identifier><identifier>PMID: 37574341</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Alcoholic Intoxication - complications ; Animals ; Burns - complications ; Burns - pathology ; episodic binge ; Ethanol ; Ethanol intoxication ; Humans ; Interleukin-6 ; lung CXCL1 ; lung granulocyte ; lung IL-6 ; lung inflammation ; Male ; Mice ; Mice, Inbred C57BL ; Pneumonia - complications</subject><ispartof>Burns, 2023-12, Vol.49 (8), p.1935-1943</ispartof><rights>2023 International Society of Burns Injuries and Elsevier Ltd</rights><rights>Copyright © 2023 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c365t-a25cadd7b5201723b25c7e7249515d538d45a36ffc7cdecaa349272f5ed829333</cites><orcidid>0000-0001-7902-5689</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37574341$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khair, Shanawaj</creatorcontrib><creatorcontrib>Walrath, Travis M</creatorcontrib><creatorcontrib>Curtis, Brenda J</creatorcontrib><creatorcontrib>Orlicky, David J</creatorcontrib><creatorcontrib>McMahan, Rachel H</creatorcontrib><creatorcontrib>Kovacs, Elizabeth J</creatorcontrib><title>Ethanol exacerbates pulmonary complications after burn injury in mice, regardless of frequency of ethanol exposures</title><title>Burns</title><addtitle>Burns</addtitle><description>Burn injuries are associated with significant morbidity and mortality, and lungs are the most common organ to fail. Interestingly, patients with alcohol intoxication at the time of burn have worse clinical outcomes, including pulmonary complications. Using a clinically relevant murine model, we have previously reported that episodic ethanol exposure before burn exacerbated lung inflammation. Specifically, intoxicated burned mice had worsened pulmonary responses, including increased leukocyte infiltration and heightened levels of CXCL1 and IL-6. Herein, we examined whether a single binge ethanol exposure before scald burn injury yields similar pulmonary responses. C57BL/6 male mice were given ethanol (1.2g/kg) 30min before a 15% total body surface area burn. These mice were compared to a second cohort given episodic ethanol binge for a total of 6 days (3 days ethanol, 4 days rest, 3 days ethanol) prior to burn injury. 24hours after burn, histopathological examination of lungs were performed. In addition, survival, and levels of infiltrating leukocytes, CXCL1, and IL-6 were quantified. Episodic and single ethanol exposure before burn decreased survival compared to burn only mice and sham vehicle mice, respectively (p<0.05). However, no difference in survival was observed between burned mice with single and episodic ethanol binge. Examination of H&E-stained lung sections revealed that regardless of ethanol binge frequency, intoxication prior to burn worsened pulmonary inflammation, evidenced by elevated granulocyte accumulation and congestion, relative to burned mice without any ethanol exposure. Levels of infiltrating granulocyte in the lungs were significantly higher in burned mice with both episodic and single ethanol intoxication, compared to burn injury only (p<0.05). In addition, there was no difference in the granulocyte count between single and ethanol binge mice with burn injury. Neutrophil chemoattractant CXCL1 levels in the lung were similarly increased following single and episodic ethanol exposure prior to burn compared to burn alone (22-fold and 26-fold respectively, p<0.05). Lastly, we assessed pulmonary IL-6, which revealed that irrespective of frequency, ethanol exposure combined with burn injury raised pro-inflammatory cytokine IL-6 in the lungs relative to burn mice. Again, we did not see find any difference in the amount of IL-6 in lungs of burned mice with single and episodic ethanol intoxication. Taken altogether, these data demonstrate that both single and episodic exposure to ethanol prior to burn injury similarly worsens pulmonary inflammation. These results suggest that ethanol-induced exacerbation of the pulmonary responses to burn injury is due to presence of ethanol at the time of injury rather than longer-term effects of ethanol exposure.
•Alcohol exposure prior to burn injury worsens clinical outcomes.•Single and episodic ethanol binge before burn similarly worsen lung inflammation.•Both ethanol exposure regimens increase lung CXCL1 and IL-6 after burn.•Ethanol presence at the time of burn is more relevant than longer ethanol exposure.</description><subject>Alcoholic Intoxication - complications</subject><subject>Animals</subject><subject>Burns - complications</subject><subject>Burns - pathology</subject><subject>episodic binge</subject><subject>Ethanol</subject><subject>Ethanol intoxication</subject><subject>Humans</subject><subject>Interleukin-6</subject><subject>lung CXCL1</subject><subject>lung granulocyte</subject><subject>lung IL-6</subject><subject>lung inflammation</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Pneumonia - complications</subject><issn>0305-4179</issn><issn>1879-1409</issn><issn>1879-1409</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9UU1v1DAQtRCILoVfgIR85NAEf8Tr5IAQqlqoVIkLnC3HnrReJXbwJBX99_V2ywou9cUazZv3Zt4j5D1nNWd8-2lX92uOWAsmZM10zVj7gmx4q7uKN6x7STZMMlU1XHcn5A3ijpWnWvaanEitdCMbviF4sdzamEYKf6yD3NsFkM7rOKVo8z11aZrH4OwSUkRqhwUy3avSEHdr6YdIp-DgjGa4sdmPgEjTQIcMv1eI7n5fwFFhTrhmwLfk1WBHhHdP_yn5dXnx8_x7df3j29X51-vKya1aKiuUs97rXgnGtZB9qTVo0XSKK69k6xtl5XYYnHYenLWy6YQWgwLfik5KeUq-HHjntZ_AO4hLtqOZc5jKbSbZYP7vxHBrbtKd4azlXHTbwvDxiSGnchAuZgroYBxthLSiEa1iWhRXeYHKA9TlhJhhOOpwZvZ5mZ15zMvs8zJMm5JXmfrw74rHmb8BFcDnAwCKUXcBskEXirPgQwa3GJ_CswIPt-WrzQ</recordid><startdate>20231201</startdate><enddate>20231201</enddate><creator>Khair, Shanawaj</creator><creator>Walrath, Travis M</creator><creator>Curtis, Brenda J</creator><creator>Orlicky, David J</creator><creator>McMahan, Rachel H</creator><creator>Kovacs, Elizabeth J</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7902-5689</orcidid></search><sort><creationdate>20231201</creationdate><title>Ethanol exacerbates pulmonary complications after burn injury in mice, regardless of frequency of ethanol exposures</title><author>Khair, Shanawaj ; Walrath, Travis M ; Curtis, Brenda J ; Orlicky, David J ; McMahan, Rachel H ; Kovacs, Elizabeth J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-a25cadd7b5201723b25c7e7249515d538d45a36ffc7cdecaa349272f5ed829333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Alcoholic Intoxication - complications</topic><topic>Animals</topic><topic>Burns - complications</topic><topic>Burns - pathology</topic><topic>episodic binge</topic><topic>Ethanol</topic><topic>Ethanol intoxication</topic><topic>Humans</topic><topic>Interleukin-6</topic><topic>lung CXCL1</topic><topic>lung granulocyte</topic><topic>lung IL-6</topic><topic>lung inflammation</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Pneumonia - complications</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khair, Shanawaj</creatorcontrib><creatorcontrib>Walrath, Travis M</creatorcontrib><creatorcontrib>Curtis, Brenda J</creatorcontrib><creatorcontrib>Orlicky, David J</creatorcontrib><creatorcontrib>McMahan, Rachel H</creatorcontrib><creatorcontrib>Kovacs, Elizabeth J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Burns</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khair, Shanawaj</au><au>Walrath, Travis M</au><au>Curtis, Brenda J</au><au>Orlicky, David J</au><au>McMahan, Rachel H</au><au>Kovacs, Elizabeth J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ethanol exacerbates pulmonary complications after burn injury in mice, regardless of frequency of ethanol exposures</atitle><jtitle>Burns</jtitle><addtitle>Burns</addtitle><date>2023-12-01</date><risdate>2023</risdate><volume>49</volume><issue>8</issue><spage>1935</spage><epage>1943</epage><pages>1935-1943</pages><issn>0305-4179</issn><issn>1879-1409</issn><eissn>1879-1409</eissn><abstract>Burn injuries are associated with significant morbidity and mortality, and lungs are the most common organ to fail. Interestingly, patients with alcohol intoxication at the time of burn have worse clinical outcomes, including pulmonary complications. Using a clinically relevant murine model, we have previously reported that episodic ethanol exposure before burn exacerbated lung inflammation. Specifically, intoxicated burned mice had worsened pulmonary responses, including increased leukocyte infiltration and heightened levels of CXCL1 and IL-6. Herein, we examined whether a single binge ethanol exposure before scald burn injury yields similar pulmonary responses. C57BL/6 male mice were given ethanol (1.2g/kg) 30min before a 15% total body surface area burn. These mice were compared to a second cohort given episodic ethanol binge for a total of 6 days (3 days ethanol, 4 days rest, 3 days ethanol) prior to burn injury. 24hours after burn, histopathological examination of lungs were performed. In addition, survival, and levels of infiltrating leukocytes, CXCL1, and IL-6 were quantified. Episodic and single ethanol exposure before burn decreased survival compared to burn only mice and sham vehicle mice, respectively (p<0.05). However, no difference in survival was observed between burned mice with single and episodic ethanol binge. Examination of H&E-stained lung sections revealed that regardless of ethanol binge frequency, intoxication prior to burn worsened pulmonary inflammation, evidenced by elevated granulocyte accumulation and congestion, relative to burned mice without any ethanol exposure. Levels of infiltrating granulocyte in the lungs were significantly higher in burned mice with both episodic and single ethanol intoxication, compared to burn injury only (p<0.05). In addition, there was no difference in the granulocyte count between single and ethanol binge mice with burn injury. Neutrophil chemoattractant CXCL1 levels in the lung were similarly increased following single and episodic ethanol exposure prior to burn compared to burn alone (22-fold and 26-fold respectively, p<0.05). Lastly, we assessed pulmonary IL-6, which revealed that irrespective of frequency, ethanol exposure combined with burn injury raised pro-inflammatory cytokine IL-6 in the lungs relative to burn mice. Again, we did not see find any difference in the amount of IL-6 in lungs of burned mice with single and episodic ethanol intoxication. Taken altogether, these data demonstrate that both single and episodic exposure to ethanol prior to burn injury similarly worsens pulmonary inflammation. These results suggest that ethanol-induced exacerbation of the pulmonary responses to burn injury is due to presence of ethanol at the time of injury rather than longer-term effects of ethanol exposure.
•Alcohol exposure prior to burn injury worsens clinical outcomes.•Single and episodic ethanol binge before burn similarly worsen lung inflammation.•Both ethanol exposure regimens increase lung CXCL1 and IL-6 after burn.•Ethanol presence at the time of burn is more relevant than longer ethanol exposure.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>37574341</pmid><doi>10.1016/j.burns.2023.07.008</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-7902-5689</orcidid></addata></record> |
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| source | Elsevier:Jisc Collections:Elsevier Read and Publish Agreement 2022-2024:Freedom Collection (Reading list) |
| subjects | Alcoholic Intoxication - complications Animals Burns - complications Burns - pathology episodic binge Ethanol Ethanol intoxication Humans Interleukin-6 lung CXCL1 lung granulocyte lung IL-6 lung inflammation Male Mice Mice, Inbred C57BL Pneumonia - complications |
| title | Ethanol exacerbates pulmonary complications after burn injury in mice, regardless of frequency of ethanol exposures |
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