Alcohol Binge Before Trauma/Hemorrhage Impairs Integrity of Host Defense Mechanisms During Recovery

Abstract

Background: Alcohol abuse, both chronic and acute, is a known modulator of immune function and is associated with increased incidence of traumatic injury. Previously, we demonstrated that acute alcohol intoxication before hemorrhagic shock impairs hemodynamic and neuroendocrine counterregulation, suppresses early lung proinflammatory cytokine expression, and increases mortality from infection during recovery. In the present study, we examined the impact of a 3-day alcohol binge on host responses during trauma/hemorrhage (TÂHem) and following overnight recovery.Methods: Chronically catheterized, adult male Sprague-Dawley rats were administered an intragastric bolus of alcohol (5 g/kg; 30% w/v) or isocaloric dextrose solution for 3 consecutive days, followed by a 2.5 g/kg dose on day 4 before undergoing full-thickness muscle-crush and fixed pressure ($40 mmHg) hemorrhage and fluid resuscitation (2.4Âtotal blood volume removed).Results: Alcohol-binge produced a 16% decrease in basal mean arterial blood pressure (MABP), reduced the total blood loss required to reach and to sustain MABP of 40 mmHg, markedly blunted the increase in circulating epinephrine and norepinephrine (20-fold and 3-fold, respectively) levels, and increased immediate mortality from TÂHem. Consistent with our previous reports, significant up-regulation in lung and spleen tumor necrosis factor (TNF)-a and interleukin (IL)-1a expression was observed immediately following TÂHem and fluid resuscitation. Only the TÂHem-induced increase in lung TNF-a was prevented by binge alcohol administration. Following overnight recovery, significant lipopolysaccharide (LPS)-stimulated release of TNF-a, IL-1a, IL-6, and IL-10 was observed in cells isolated from blood and the alveolar and pleural compartments from all experimental groups. While TÂHem did not prevent LPS-induced release of TNF-a, IL-1a, IL-6, or IL-10 at 6 or 24 hours, alcohol binge suppressed TNF-a, IL-1 and IL-6 release, without altering IL-10 response in cells isolated from blood and pleural compartment. No significant modulation of alveolar macrophage response was observed following alcohol binge and TÂHem.Conclusions: These results indicate that a 3-day alcohol binge results in hemodynamic instability associated with attenuated neuroendocrine activation and increased mortality during TÂHem as well as sustained suppression of the proinflammatory cytokine response of blood and pleural-derived cells to a ''second-hit'' inflammatory challenge. As a result, we speculate that the net shift toward an antiinflammatory state may contribute to enhanced susceptibility to infection during the recovery period.

Risk Score to Predict Hospital-Acquired Pneumonia After Spontaneous Intracerebral Hemorrhage

“…Considerable prior studies have detailed the deleterious effect of alcohol abuse on host immune system, as would result in a higher incidence and severity of infection. 35,36 Although infratentorial ICH, hematoma volume, and intraventricular extension have been shown to be risk factors for poor outcome after ICH, 21,22 the underlying molecular mechanisms for increased risk of developing SAP after ICH need to be further investigated.…”

“…Considerable prior studies have detailed the deleterious effect of alcohol abuse on host immune system, as would result in a higher incidence and severity of infection. 35,36 Although infratentorial ICH, hematoma volume, and intraventricular extension have been shown to be risk factors for poor outcome after ICH, 21,22 the underlying molecular mechanisms for increased risk of developing SAP after ICH need to be further investigated.For a clinical grading scale to become effective and widely used, it must be reliable, accurate, and practicable. For reliability, the ICH-APSs were developed based on a large ICH cohort, which included consecutive patients who were outside clinical trials and were more reflective of real-world clinical practice.…”

Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine

“…Alcohol has been shown to play a role of immunomodulatory agent: acute alcohol consumption has inhibitory effects on the release of pro-inflammatory cytokines, while chronic alcohol consumption lead to a significantly prolonged response of inflammatory cells [64]. In experimental models, binge drinking before trauma resulted in attenuated levels of TNFα, IL-1, and IL-6 [65]. In human alcoholics, the levels of the immunosuppressive cytokine IL-10 were significantly increased over those in non-alcoholic individuals after major surgical intervention [66].…”

In vitroandin vivomodels of acute alcohol exposure

“…AAA leads to insufficient immune system responses to infections; such deficiency was observed both in organ-specific [67][68][69] and systemic infections [70][71][72] . Acute alcohol intoxication impairs the ability of the host to counteract hemorrhagic shock [73] , augments corticosteroid release [74] and delays wound healing [75][76][77][78] , thus contributing to higher morbidity and mortality [79] and prolonged recovery from trauma [80] . The pathogenesis of AAA effects on human health is not fully understood.…”

“…The vertebrate AAA models are widely used in research of biomedical effects of AAA, including brain [23][24][25][26][27][28][29][30]116] , gastrointestinal [38][39][40][41][42][43][44][46][47][48][64][65][66]154] , vascular [73,153] , muscle [97] and immune [68][69][70][71][72]74] systems.…”