Ethanol Intoxication Alleviates the Inflammatory Response of Remote Organs to Experimental Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) may cause damage to distant organs. Acute ethanol intoxication (EI) induces complex local and systemic anti-inflammatory effects and influences the early outcomes of traumatized patients. Here, we evaluated its effects on the BI-induced expression of local inflammatory mediators in the trauma-remote organs the lungs and liver. Male mice were exposed to ethanol as a single oral dose (5g·kg–1, 32%) before inducing a moderate blunt TBI. Sham groups underwent the same procedures without TBI. Ether 3 or 6h after the TBI, the lung and liver were collected. The gene expression of HMGB1, IL-6, MMP9, IL-1β, and TNF as well as the homogenate protein levels of receptor for advanced glycation end products (RAGE), IL-6, IL-1β, and IL-10 were analyzed. Liver samples were immunohistologically stained for HMGB1. EI decreased the gene expressions of the proinflammatory markers HMGB1, IL-6, and MMP9 in the liver upon TBI. In line with the reduced gene expression, the TBI-induced protein expression of IL-6 in liver tissue homogenates was significantly reduced by EI at 3h after TBI. While the histological HMGB1 expression was enhanced by TBI, the RAGE protein expression in the liver tissue homogenates was diminished after TBI. EI reduced the histological HMGB1 expression and enhanced the hepatic RAGE protein expression at 6h post TBI. With regard to the lungs, EI significantly reduced the gene expressions of HMGB1, IL-6, IL-1β, and TNF upon TBI, without significantly affecting the protein expression levels of inflammatory markers (RAGE, IL-6, IL-1β, and IL-10). At the early stage of TBI-induced inflammation, the gene expression of inflammatory mediators in both the lungs and liver is susceptible to ethanol-induced remote effects. Taken together, EI may alleviate the TBI-induced pro-inflammatory response in the trauma-distant organs, the lungs and liver, via the HMGB1-RAGE axis.

Inflammatory Predictors of Prognosis in Patients with Traumatic Cerebral Haemorrhage: Retrospective Study

“…The percentage of patients being intoxicated at the time of admission ranges between 30% and 60% in different studies [16]. According to Xu et al [47], alcohol may alleviate the TBI-induced pro-inflammatory response. In our study, 37% of all the patients with TICH were under the influence of alcohol, but their values of NLR and SII did not differ when compared to other patients.…”

Fast maturation of splenic dendritic cells upon TBI is associated with FLT3/FLT3L signaling

“…Importantly, EI also rapidly (already at 3h) dampens the systemic inflammatory response triggered by TBI. In particular, in murineTBI, levels of HMGB1 and IL-6 are decreased in the liver of mice subject to EI/TBI compared to TBI alone (but IL-1β is actually upregulated; [10]) In contrast, in the lungs EI decreases the levels of HMGB1, IL-6, IL-1β and TNF-α, while moderately increasing IL-10 [10]. In line with this evidence, EI is associated with reduced systemic IL-6 levels and less pronounced leukocytosis in human TBI patients [109] and in patients after major traumas (including TBI; [110]), as well as increased levels of IL-10 [111].…”

“…In particular, HMGB1, an alarmin located in the nucleus of neurons and glial cells and released upon brain tissue disruption [92, 93], is highly and rapidly elevated in serum after TBI [94, 95]. HMGB1 has been found to contribute not only to local neuroinflammation upon neurotrauma [96, 97] but it is also induced in non-cerebral tissues post TBI and contributes to the subsequent systemic inflammation following TBI [10]. Notably, HMGB1 is also a major inducer of DC maturation, an effect that appears to be relevant in the context of lung injury (through mTOR signaling; [98]) and in liver injury [99].…”

“…The systemic response to TBI is characterized by inflammation and, at the same time, a net systemic immunosuppression [4][5][6]. Although brain injury results in a systemic increase of inflammatory mediators and cytokines in both patients [7][8][9] and rodent models of TBI [10][11][12], there remains ample of evidence pointing towards a systemic immunosuppression post TBI, with a decrease in immune cells in the periphery [13][14][15][16][17][18]. Generalized immunosuppression is highly relevant on clinical grounds, since it may contribute to an enhanced vulnerability to infections observed after severe tissue injury.…”

The future of basic science in orthopaedics and traumatology: Cassandra or Prometheus?

“…Furthermore, the better definition of the inflicted injury on well-defined anatomical regions helps to standardize the injury pattern and thus provides a better if not superior comparison with specific human situations [ 164 ]. Another development towards translational validity is the increasing consideration of various co-morbidities and their adequate modelling such as diabetes, osteoporosis, smoking, alcohol, atherosclerosis or chronic obstructive pulmonary disease in the context of trauma [ 165 – 167 ].…”