Alcohol binge before trauma/hemorrhage impairs integrity of host defense mechanisms during recovery.
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 (T x Hem) 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 (approximately 40 mmHg) hemorrhage and fluid resuscitation (2.4 x total 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 T x Hem. Consistent with our previous reports, significant up-regulation in lung and spleen tumor necrosis factor (TNF)-alpha and interleukin (IL)-1alpha expression was observed immediately following T x Hem and fluid resuscitation. Only the T x Hem-induced increase in lung TNF-alpha was prevented by binge alcohol administration. Following overnight recovery, significant lipopolysaccharide (LPS)-stimulated release of TNF-alpha, IL-1alpha, IL-6, and IL-10 was observed in cells isolated from blood and the alveolar and pleural compartments from all experimental groups. While T x Hem did not prevent LPS-induced release of TNF-alpha, IL-1alpha, IL-6, or IL-10 at 6 or 24 hours, alcohol binge suppressed TNF-alpha, 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 T x Hem.


CONCLUSIONS
These results indicate that a 3-day alcohol binge results in hemodynamic instability associated with attenuated neuroendocrine activation and increased mortality during T x Hem 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 anti-inflammatory state may contribute to enhanced susceptibility to infection during the recovery period.
Greiffenstein
Patrick
P
Department of Physiology and Alcohol Research Center, LSU Health Sciences Center, New Orleans, Louisiana 70112, USA.
Mathis
Keisa W
KW
Stouwe
Curtis Vande
CV
Molina
Patricia E
PE
D000428:Alcohol Drinking / Q000097:blood / Q000276:immunology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D020201:Brain Hemorrhage, Traumatic / Q000097:blood / Q000150:complications / Q000276:immunology*; D001930:Brain Injuries / Q000097:blood / Q000150:complications / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016887:Cardiopulmonary Resuscitation; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D000431:Ethanol / Q000097:blood; D006339:Heart Rate / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000187:drug effects; D009638:Norepinephrine / Q000097:blood; D010994:Pleura / Q000473:pathology; D011650:Pulmonary Alveoli / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012769:Shock / Q000503:physiopathology
D016207:Cytokines; D008070:Lipopolysaccharides; D000431:Ethanol; D003345:Corticosterone; D009638:Norepinephrine; D004837:Epinephrine