Decreased pulmonary inflammation after ethanol exposure and burn injury in intercellular adhesion molecule-1 knockout mice.
Clinical and laboratory evidence suggests that alcohol consumption dysregulates immune function. Burn patients who consume alcohol before their injuries demonstrate higher rates of morbidity and mortality, including acute respiratory distress syndrome, than patients without alcohol at the time of injury. Our laboratory observed higher levels of proinflammatory cytokines and leukocyte infiltration in the lungs of mice after ethanol exposure and burn injury than with either insult alone. To understand the mechanism of the increased pulmonary inflammatory response in mice treated with ethanol and burn injury, we investigated the role of intercellular adhesion molecule (ICAM)-1. Wild-type and ICAM-1 knockout (KO) mice were treated with vehicle or ethanol and subsequently given a sham or burn injury. Twenty-four hours postinjury, lungs were harvested and analyzed for indices of inflammation. Higher numbers of neutrophils were observed in the lungs of wild-type mice after burn and burn with ethanol treatment. This increase in pulmonary inflammatory cell accumulation was significantly lower in the KO mice. In addition, levels of KC, interleukin-1beta, and interleukin-6 in the lung were decreased in the ICAM-1 KO mice after ethanol exposure and burn injury. Interestingly, no differences were observed in serum or lung tissue content of soluble ICAM-1 24 hours postinjury. These data suggest that upregulation of adhesion molecules such as ICAM-1 on the vascular endothelium may play a critical role in the excessive inflammation seen after ethanol exposure and burn injury.
Bird
Melanie D
MD
Department of Surgery, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Morgan
Michelle O
MO
Ramirez
Luis
L
Yong
Sherri
S
Kovacs
Elizabeth J
EJ
D000704:Analysis of Variance; D000818:Animals; D002056:Burns / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D000431:Ethanol / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism; D011014:Pneumonia / Q000378:metabolism*
D007375:Interleukin-1; D015850:Interleukin-6; D018799:Intercellular Adhesion Molecule-1; D000431:Ethanol