Alcohol‑induced attenuation of post‑traumatic inflammation is�not necessarily liver‑protective following trauma/hemorrhage

Abstract

due to their high prevalence, blunt chest trauma (TxT) and hemorrhagic shock have a significant influence on the outcomes of trauma patients, causing severe modulations of the immune system and high mortality rates. Alcohol consumption in trauma patients has a high clinical impact. Studies investigating the timing of alcohol intoxication prior to trauma are limited, although there are two typical scenarios regarding alcohol consumption: Acute ('drink and drive scenario') and sub-acute ('evening binge drinking'). Therefore, the present study investigated the influence of either an acute or sub-acute alcohol-drinking scenario in an in vivo model of TxT and hemorrhagic shock, focusing on liver inflammation and outcomes. At 12 h (sub-acute) or 2 h (acute) before the experiment, female Lewis rats received a single oral dose of alcohol (ethanol, EtOH) or saline (Nacl, ctrl), followed by TxT, hemorrhagic shock (35±3 mm Hg) and resuscitation (H/R). The animals were either sacrificed 2 h later or their survival was determined for 72 h. The results revealed that EtOH induced significant fatty changes in the liver. TxT + H/R-induced increases in the gene expression of interleukin (IL)-6 and intercellular adhesion molecule-1 and the protein expression of tumor necrosis factor (TNF)-α and IL-1β were significantly reduced in both EtOH groups compared with those in the corresponding TxT + H/R ctrl groups. The local presence of IL-10-expressing cells in the liver was significantly increased following TxT + H/R in all groups, although the sub-acute EtOH TxT + H/R group had a significantly higher proportion of IL-10-positive cells compared with all other groups. Stimulating peripheral whole blood with lipopolysaccharide led to significantly lower levels of TNF-α release in the sub-acute EtOH group compared with the levels in all other groups. Significant TxT + H/R-induced increases in liver transaminases and liver damage were most prominent in the sub-acute EtOH group. The TxT + H/R EtOH group exhibited the lowest levels of glucose. There were no significant differences in mortality rate among the TxT + H/R groups. The data obtained indicates that the severity of liver damage following TxT + H/R may depend on the timing of alcohol consumption and severity of trauma, but also on the balance between pro-and anti-inflammatory responses.

Different experimental multiple trauma models induce comparable inflammation and organ injury

“…This in turn contributed significantly to the injury of epithelial cells with subsequent capillary breakdown and microcirculatory disturbances [42][43][44][45][46] . Other models including chest trauma have confirmed among others the pathomechanistic importance of the proinflammatory mediators IL-6 and also CXCL1 for the development of lung damage 40,41,47,48 . Furthermore, organ injury is widely dependent on the presence of inflammatory cells in the tissue.…”

“…IL-6, IL-8, CXCL family members) and anti-inflammatory (e.g. IL-10) mediators were experimentally and clinically demonstrated to play important roles in this damage response to traumatic injury, or to indicate outcomes 6,7,40,41 .…”

“…In the end, hematoxylin was used for counterstaining of the samples. An independent examiner (KK) determined histological tissue damage of HE-stained sections of the various experimental groups in a blinded manner as described before 40,41 . Lung sections were examined for interstitial neutrophilic infiltration and for interstitial thickness (alveolar space), whereas liver sections were evaluated for infiltration with inflammatory cells (neutrophilic granulocytes) via the Ly6G staining (Anti-Ly6g antibody [RB6-8C5] (ab25377)) and necrosis.…”

Acute Alcohol Intoxication Modulates Monocyte Subsets and Their Functions in a Time-Dependent Manner in Healthy Volunteers

“…50 µl heparinized blood was added to 450 µl RPMI 1640 media with supplements [100 UI/ml penicillin, 100 µg/ml streptomycin, 0.1 mg/ml gentamycin, 20 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, 10% heat-inactivated fetal bovine serum (FBS)] and LPS at final concentration of 10 µg/ml ( 20 ). Subsequently, the samples were incubated at 37°C and 5% CO 2 for 24 hours.…”

“…gentamycin, 20 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, 10% heat-inactivated fetal bovine serum (FBS)] and LPS at final concentration of 10 µg/ml (20). Subsequently, the samples were incubated at 37°C and 5% CO 2 for 24 hours.…”