Acute alcohol intoxication increases interleukin-18-mediated neutrophil infiltration and lung inflammation following burn injury in rats.
In this study, we examined whether IL-18 plays a role in lung inflammation following alcohol (EtOH) and burn injury. Male rats ( approximately 250 g) were gavaged with EtOH to achieve a blood EtOH level of approximately 100 mg/dl before burn or sham injury ( approximately 12.5% total body surface area). Immediately after injury, rats were treated with vehicle, caspase-1 inhibitor AC-YVAD-CHO to block IL-18 production or with IL-18 neutralizing anti-IL-18 antibodies. In another group, rats were treated with anti-neutrophil antiserum approximately 16 h before injury to deplete neutrophils. On day 1 after injury, lung tissue IL-18, neutrophil chemokines (CINC-1/CINC-3), ICAM-1, neutrophil infiltration, MPO activity, and water content (i.e., edema) were significantly increased in rats receiving a combined insult of EtOH and burn injury compared with rats receiving either EtOH intoxication or burn injury alone. Treatment of rats with caspase-1 inhibitor prevented the increase in lung tissue IL-18, CINC-1, CINC-3, ICAM-1, MPO activity, and edema following EtOH and burn injury. The increase in lung IL-18, MPO, and edema was also prevented in rats treated with anti-IL-18 antibodies. Furthermore, administration of anti-neutrophil antiserum also attenuated the increase in lung MPO activity and edema, but did not prevent the increase in IL-18 levels following EtOH and burn injury. These findings suggest that acute EtOH intoxication before burn injury upregulates IL-18, which in turn contributes to increased neutrophil infiltration. Furthermore, the presence of neutrophils appears to be critical for IL-18-meditaed increased lung tissue edema following a combined insult of EtOH and burn injury.
Li
Xiaoling
X
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Kovacs
Elizabeth J
EJ
Schwacha
Martin G
MG
Chaudry
Irshad H
IH
Choudhry
Mashkoor A
MA
D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000818:Animals; D002056:Burns / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004487:Edema / Q000201:enzymology / Q000473:pathology; D000431:Ethanol / Q000633:toxicity; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology*; D020382:Interleukin-18 / Q000502:physiology*; D008168:Lung / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D020382:Interleukin-18; D000431:Ethanol; D009195:Peroxidase