Acute alcohol intake impairs lung inflammation by changing pro- and anti-inflammatory mediator balance

Abstract

Previous studies have shown that alcohol (EtOH) intoxication impairs lung immunity by affecting cytokines pivotal to the inflammatory process. The objective of this study was to test the hypothesis that acute alcohol intoxication impairs lung innate immunity by down-regulating the expression of pro-inflammatory mediators while simultaneously up-regulating anti-inflammatory mediators. EtOH was administered to the mice 0.5 h prior to an intra-tracheal injection of E. coli lipopolysaccharide (LPS). The animals were killed either 4 or 24 h after LPS to recover plasma, lungs and bronchoalveolar lavage fluid. Lung inflammatory cytokines TNF-α, IL-1β, IL-6, MIF, IL-10, TGF-β and receptors for TNF-α, IL-1β, IL-6 and TGF-β as well as gp130 and corticosterone levels were evaluated at mRNA and protein level. While the mRNA expression and the soluble TNF-Rp55 levels were significantly up-regulated by EtOH, LPS-induced TNF-α activity, TNF-Rp55 mRNA expression and soluble TNF-Rp55 levels were significantly suppressed. The LPS-induced expression of IL-1β, IL-6, MIF, gp130, and receptors IL-1RI, IL-1RII and IL-6Rα were also significantly impaired by EtOH. EtOH increased significantly basal IL-10 activity at 3 h, which continued to remain elevated even at 24 h. The EtOH effect on IL-10 activity persisted even in LPS-challenged mice. EtOH and LPS augmented lung corticosterone levels independently of each other. EtOH suppressed up-regulation of TGF-β1 mRNA expression by LPS and blocked completely LPSinduced TGF-β1 secretion. In conclusion, the data suggest that the suppression of acute lung inflammation by EtOH intoxication is largely due to impairment by EtOH of pro-inflammatory cytokine signaling at the levels of cytokine expression and secretion as well as receptor expression and soluble receptor activity. The augmentation by EtOH of anti-inflammatory mediators' secretion most likely shifts the cytokine balance in the anti-inflammatory direction.

Neuroimmune Interface in the Comorbidity between Alcohol Use Disorder and Major Depression

“…Acute heavy alcohol consumption (e.g., ≥3 g/kg), even in a single dose, inhibits inflammatory cell activation (28–30). Upon LPS challenge, alcohol-primed mice suppressed lung TNF-α activity, TNF-Rp55 mRNA expression, and soluble TNF-Rp55 levels (31). Ethanol suppressed LPS-induced expression of IL-1, IL-6, and their receptors while significantly upregulating IL-10 levels.…”

“…Animal studies have demonstrated that an anti-inflammatory effect of acute binge drinking ensues already in the first hour and lasts beyond ethanol elimination from the body (22, 31). The same finding was replicated in humans 13 h after intake of 1.5 g/kg of alcohol (35).…”

Laboratory Models Available to Study Alcohol‐Induced Organ Damage and Immune Variations: Choosing the Appropriate Model

“…Alcohol (20% w/v) is administered either as an oral gavage directly into the stomach or as a single bolus injection given IP [Plackett and Kovacs, 2008; D’Souza El-Guindy et al 2007; Nelson et al 1989]. The control animals receive an equivalent volume of the vehicle (water or saline).…”

“…For example, peak blood alcohol levels will be achieved faster when alcohol is administered IV vs. IP or via an oral gavage and on an empty stomach. It is also important to note that forced alcohol administration can initiate a stress response, manifested by an increased release of glucocorticoids, which can be immunosuppressive [Collier et al, 2000; Meadows et al, 1993a; D’Souza El-Guindy et al, 2007]. Unlike the IP or IV methods, the oral gavage method of administering alcohol to laboratory animals is closer to human drinking; however, if not performed correctly, it has the probability of introducing a greater stress response than the IP or IV methods.…”

“…Yet, when the intoxicated animals are subjected to an in vivo immune challenge or a traumatic injury, functions such as the expression and secretion of many early innate immune response cytokines, the recruitment of inflammatory cells to the insult site, and carbohydrate metabolism are mostly suppressed [D’Souza El-Guindy et al, 2007; Zhang et al, 1997; Goral et al, 2008; Molina et al, 1991]. In vivo alcohol administration also affects ex-vivo response of immune cells to immune stimuli [Szabo and Mandrekar, 2009].…”