Adverse Clinical Outcomes Associated With Elevated Blood Alcohol Levels at the Time of Burn Injury

Silver, Geoffrey M.; Albright, Joslyn M.; Schermer, Carol R.; Halerz, Marcia; Conrad, Peggie; Ackerman, Paul D.; Lau, Linda; Emanuele, Mary Ann; Kovacs, Elizabeth J.; Gamelli, Richard L.

doi:10.1097/bcr.0b013e31818481bc

Cited by 73 publications

(79 citation statements)

References 32 publications

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“…Approximately one million burn injuries are reported every year within the United States, and nearly half of them occur in individuals who are under the influence of alcohol/ethanol (EtOH) (1)(2)(3). Studies have shown that patients who are intoxicated at the time of injury are more susceptible to infection and have a higher incidence of mortality compared with burn patients who have not consumed EtOH at the time of injury (2,4,5). Similarly, findings from experimental studies have also shown that EtOH intoxication before burn injury exacerbates the suppression of immunity, impairs intestinal barrier function, and increases bacterial translocation relative to either EtOH intoxication or burn injury alone (6)(7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 69%

Interleukin-18 Delays Neutrophil Apoptosis following Alcohol Intoxication and Burn Injury

Akhtar

Kovacs

et al. 2010

Mol Med

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Section: Introductionmentioning

confidence: 69%

Interleukin-18 Delays Neutrophil Apoptosis following Alcohol Intoxication and Burn Injury

Akhtar

Kovacs

et al. 2010

Mol Med

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“…Nearly one million burn injuries are reported in the United States every year, and 50% of these injuries occur in individuals under the influence of alcohol/ethanol (EtOH) (4)(5)(6)(7)(8). Studies indicate that intoxicated patients have higher rates of septic complications, longer hospital stays and increased mortality compared with patients who have a similar extent of burn injury but did not consume EtOH before injury (7)(8)(9)(10)(11). There is evidence that EtOH intoxication combined with burn injury abrogates the host immune system.…”

Section: Introductionmentioning

confidence: 99%

Activation of Toll-Like Receptor 2 Prevents Suppression of T-Cell Interferon γ Production by Modulating p38/Extracellular Signal-Regulated Kinase Pathways following Alcohol and Burn Injury

Rendón

Akhtar

et al. 2012

Mol Med

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Recent studies indicate that toll-like receptors (TLRs) are expressed on T cells and that these receptors directly or indirectly activate the adaptive immune system. We have shown previously that acute alcohol/ethanol (EtOH) intoxication combined with burn injury suppresses mesenteric lymph node (MLN) T-cell interleukin-2 (IL-2) and interferon γ (IFN-γ) production. We examined whether direct stimulation of T cells with TLR2, 4, 5 and 7 agonists modulates CD3-mediated T-cell IL-2/IFN-γ release following EtOH and burn injury. Male mice were gavaged with EtOH (2.9 gm/kg) 4 h prior to receiving an ~12.5% total body surface area sham or full-thickness burn injury. Animals were killed on d 1 after injury and T cells were purified from MLN and spleens. T cells were cultured with plate-bound anti-CD3 in the presence or absence of various TLR ligands. Although TLR2, 4 and 5 agonists potentiate anti-CD3-dependent IFN-γ by T cells, the TLR2 agonist alone induced IFN-γ production independent of CD3 stimulation. Furthermore, T cells were treated with inhibitors of myeloid differentiation primary response protein 88 (MyD88), TIR domain-containing adaptor protein (TIRAP), p38 and/or extracellular signal-regulated kinase (ERK) to determine the mechanism by which TLR2 mediates IL-2/IFN-γ production. IL-2 was not influenced by TLR agonists. MyD88 and TIRAP inhibitory peptides dose-dependently diminished the ability of T cells to release IFN-γ. p38 and ERK inhibitors also abolished TLR2-mediated T-cell IFN-γ. Together, our findings suggest that TLR2 directly modulates T-cell IFN-γ production following EtOH and burn injury, independent of antigen-presenting cells. Furthermore, we demonstrated that MyD88/TIRAP-dependent p38/ERK activation is critical to TLR2-mediated T-cell IFN-γ release following EtOH and burn injury.

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“…The practice of consuming enough alcohol to bring the blood alcohol concentration to Ն0.08%, known as binge drinking, is an increasingly prevalent form of intoxication (39) and the characteristic consumption pattern among patients presenting with traumatic injury, including burns (46). Approximately half of adult burn patients are intoxicated at the time of admission, and these patients have worse clinical outcomes than individuals who sustain similar injuries without alcohol exposure (23,29,48). Specifically, they are twice as likely to acquire an infection, undergo 60% more surgical procedures, require more days on mechanical ventilation, and stay longer in the intensive care unit (6,48).…”

mentioning

confidence: 99%

An alteration of the gut-liver axis drives pulmonary inflammation after intoxication and burn injury in mice

Chen

Zahs

Brown

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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imately half of all adult burn patients are intoxicated at the time of their injury and have worse clinical outcomes than those without prior alcohol exposure. This study tested the hypothesis that intoxication alters the gut-liver axis, leading to increased pulmonary inflammation mediated by burn-induced IL-6 in the liver. C57BL/6 mice were given 1.2 g/kg ethanol 30 min prior to a 15% total body surface area burn. To restore gut barrier function, the specific myosin light chain kinase inhibitor membrane-permeant inhibitor of kinase (PIK), which we have demonstrated to reduce bacterial translocation from the gut, was administered 30 min after injury. Limiting bacterial translocation with PIK attenuated hepatic damage as measured by a 47% reduction in serum alanine aminotransferase (P Ͻ 0.05), as well as a 33% reduction in hepatic IL-6 mRNA expression (P Ͻ 0.05), compared with intoxicated and burn-injured mice without PIK. This mitigation of hepatic damage was associated with a 49% decline in pulmonary neutrophil infiltration (P Ͻ 0.05) and decreased alveolar wall thickening compared with matched controls. These results were reproduced by prophylactic reduction of the bacterial load in the intestines with oral antibiotics before intoxication and burn injury. Overall, these data suggest that the gut-liver axis is deranged when intoxication precedes burn injury and that limiting bacterial translocation in this setting attenuates hepatic damage and pulmonary inflammation.

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Adverse Clinical Outcomes Associated With Elevated Blood Alcohol Levels at the Time of Burn Injury

Cited by 73 publications

References 32 publications

Interleukin-18 Delays Neutrophil Apoptosis following Alcohol Intoxication and Burn Injury

Interleukin-18 Delays Neutrophil Apoptosis following Alcohol Intoxication and Burn Injury

Activation of Toll-Like Receptor 2 Prevents Suppression of T-Cell Interferon γ Production by Modulating p38/Extracellular Signal-Regulated Kinase Pathways following Alcohol and Burn Injury

An alteration of the gut-liver axis drives pulmonary inflammation after intoxication and burn injury in mice

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