Effects of Multiday Ethanol Intoxication on Postburn Inflammation, Lung Function, and Alveolar Macrophage Phenotype

Burn patients who consumed alcohol before injury have worse clinical outcomes, including longer hospital stays, increased ventilator days, and more respiratory infections. Most alcohol consumers are binge drinkers and not chronic alcoholics, and binge drinking patterns fluctuate over the week, with consecutive days of drinking over the weekend followed by relative abstinence during the week. We used a murine model simulating this drinking pattern in the context of burn injury. Mice were given ethanol for 3 days, rested for 4 days, given ethanol for 3 more days, followed by a sham or 15% total body surface area full-thickness burn. We previously demonstrated that mice exposed to the combined insult exhibited respiratory dysfunction and 50% mortality, with those that succumbed to injury dying between 24 and 72 h, thus identifying a therapeutic intervention window. Our goal herein is to characterize inflammatory and respiratory parameters during this critical time frame. We saw that mice exposed to the combined insult had the highest circulating and pulmonary cytokine levels at 24 h, which were normalized by 72 h in survivors. Alveolar macrophage activation was observed at 24 h in burned mice, regardless of intoxication (P < 0.05). However, at 72 h, alveolar macrophages from intoxicated burned mice had elevated CD206, relative to controls (P < 0.05), indicative of an anti-inflammatory phenotype. Taken together, these findings suggest that although lung function and inflammation are normalized by 72 h, the alterations in alveolar macrophage phenotype shed light on a potential mechanism underlying increased infection susceptibility in intoxicated burn patients.