CHRONIC ALCOHOL EXPOSURE ENHANCES PULMONARY NEUTROPHIL RECRUITMENT IN RESPONSE TO INTRA TRACHEAL ENDOTOXIN.
Document Type
Presentation
Start Date
22-10-2010 3:00 PM
End Date
22-10-2010 4:30 PM
Description
PURPOSE: Chronic alcohol abuse is a major health problem in the U.S. Animal studies have shown that chronic alcohol ingestion predisposes the lung to injury, and clinical data implicate alcohol abuse as a risk factor in the development of the acute respiratory distress syndrome (ARDS). Neutrophil (PMN) influx is a histologic hallmark of ARDS and is essential to ARDS development. Acute alcohol intoxication in mice impairs alveolar PMN recruitment to the lung during local airway challenge with bacterial lipopolysaccharide (LPS), but the effect of chronic ethanol administration on alveolar PMN influx in this model are not well-characterized.
METHODS: Female C57BL/6 mice were fed a Lieber-DiCarli liquid ethanol diet (30% of calories as ethanol) for 5 days a week and received ethanol in drinking water (25% v/v) plus chow on weekends for 8 weeks. Control animals were pair fed by cage to equalize caloric intake. E. coli LPS (10 μg) was administered intratracheally (i.t.), and animals were then sacrificed for bronchoalveolar lavage (BAL) and lung tissue harvesting.
RESULTS: Alveolar macrophage populations were similar between groups prior to LPS challenge. 24 hours after i.t. LPS injection, alcohol feeding significantly increased the number of PMN in BAL fluid compared to control animals. This result was associated with significantly greater increases in inflammatory cytokine (TNF-a, IL-1~, IL-6, G-CSF, GM-CSF, IL-17) and chemokine (MIP-2, MCP-1) production in the lung tissue of ethanol-fed mice, as well as greater total protein leak into the alveolar space compared to controls. Plasma levels of IL-6, G-CSF, and MCP-1 were higher in ethanol-fed mice, and qRT-PCR of lung tissue mRNA confirmed the exaggerated IL-6 induction in alcohol-fed animals occurs at the transcriptional level.
CONCLUSIONS: Chronic alcohol feeding enhances PMN recruitment into the lung following airway LPS challenge, possibly by increasing the local expression of cytokines known to increase PMN recruitment (e.g. MIP-2) and/or survival (e.g. GCSF). These data suggest exaggerated PMN recruitment as a possible mechanism by which chronic alcohol abuse potentiates the lung's inflammatory response to bacterial challenge.
Recommended Citation
Teng, Xu Sophie, "CHRONIC ALCOHOL EXPOSURE ENHANCES PULMONARY NEUTROPHIL RECRUITMENT IN RESPONSE TO INTRA TRACHEAL ENDOTOXIN." (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 23.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/poster2/23
CHRONIC ALCOHOL EXPOSURE ENHANCES PULMONARY NEUTROPHIL RECRUITMENT IN RESPONSE TO INTRA TRACHEAL ENDOTOXIN.
PURPOSE: Chronic alcohol abuse is a major health problem in the U.S. Animal studies have shown that chronic alcohol ingestion predisposes the lung to injury, and clinical data implicate alcohol abuse as a risk factor in the development of the acute respiratory distress syndrome (ARDS). Neutrophil (PMN) influx is a histologic hallmark of ARDS and is essential to ARDS development. Acute alcohol intoxication in mice impairs alveolar PMN recruitment to the lung during local airway challenge with bacterial lipopolysaccharide (LPS), but the effect of chronic ethanol administration on alveolar PMN influx in this model are not well-characterized.
METHODS: Female C57BL/6 mice were fed a Lieber-DiCarli liquid ethanol diet (30% of calories as ethanol) for 5 days a week and received ethanol in drinking water (25% v/v) plus chow on weekends for 8 weeks. Control animals were pair fed by cage to equalize caloric intake. E. coli LPS (10 μg) was administered intratracheally (i.t.), and animals were then sacrificed for bronchoalveolar lavage (BAL) and lung tissue harvesting.
RESULTS: Alveolar macrophage populations were similar between groups prior to LPS challenge. 24 hours after i.t. LPS injection, alcohol feeding significantly increased the number of PMN in BAL fluid compared to control animals. This result was associated with significantly greater increases in inflammatory cytokine (TNF-a, IL-1~, IL-6, G-CSF, GM-CSF, IL-17) and chemokine (MIP-2, MCP-1) production in the lung tissue of ethanol-fed mice, as well as greater total protein leak into the alveolar space compared to controls. Plasma levels of IL-6, G-CSF, and MCP-1 were higher in ethanol-fed mice, and qRT-PCR of lung tissue mRNA confirmed the exaggerated IL-6 induction in alcohol-fed animals occurs at the transcriptional level.
CONCLUSIONS: Chronic alcohol feeding enhances PMN recruitment into the lung following airway LPS challenge, possibly by increasing the local expression of cytokines known to increase PMN recruitment (e.g. MIP-2) and/or survival (e.g. GCSF). These data suggest exaggerated PMN recruitment as a possible mechanism by which chronic alcohol abuse potentiates the lung's inflammatory response to bacterial challenge.
Comments
See abstract book page 67