Ethanol and cytokine secretion

doi:10.1016/0741-8329(92)90080-T

Alcohol

Volume 9, Issue 6, November–December 1992, Pages 455-458

https://doi.org/10.1016/0741-8329(92)90080-T Get rights and content

Abstract

Cytokines are regulatory polypeptides secreted during the generation of an immune or inflammatory response by lymphocytes, cells of the monocyte/macrophage series, and a variety of other cell types. Alterations in the production, site of action, or metabolism of cytokines by exogenous factors, such as ethanol (EtOH), may have deleterious effects on the immune system as a whole. EtOH has been implicated in the onset of a variety of immune defects in vivo including effects on the production of cytokines critically involved in inflammatory responses (tumor necrosis factor, interleukin 1 and interleukin 6). In this review, we examine current knowledge regarding the effects of EtOH on the release of cytokines in humans and in animal models, in vitro and in vivo, which may help to elucidate the adverse actions of EtOH on mammalian immune systems.

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While both NF-κB function and RelA expression were upregulated shortly after ethanol administration (Rulten et al., 2006), the increase appears to be transient since it is not sustained following sub-chronic ethanol treatment (a 9% ethanol-containing liquid diet for 15 days) (Mittal et al., 1999). Although cellular and molecular mechanisms by which alcohol causes brain damage are not fully understood, numerous studies suggest a role of inflammatory processes (Altura et al., 2002; Blanco et al., 2005; Davis and Syapin, 2004; Lee et al., 2004; Martinez et al., 1992; Minambres et al., 2006; Nelson et al., 1989; Valles et al., 2004). At the transcription level, inflammation is primarily regulated by NF-κB and related factors in a variety of cells and tissues.
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Immediate and prolonged effects of alcohol exposure on the activity of the hypothalamic-pituitary-adrenal axis in adult and adolescent rats
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Indeed, the ability of LPS to activate PVN CRF neurons further supports this concept (Lee et al., 1995). Furthermore, a review of potential interactions between alcohol and cytokine secretion (Martinez et al., 1992) lead to the concept that alcohol might release cytokines, which led our laboratory to investigate the hypothesis that the stimulatory effect of alcohol on the HPA axis might, at least in part, depend on endogenous cytokine release. In particular, we explored the effects of acute pretreatment with alcohol upon the release of ACTH, corticosterone and pro-inflammatory cytokines (TNFα and IL-6) following endotoxicity (LPS administration), and found that the drug increased the corticosterone, but not the ACTH response to LPS (Rivier, 1999).
Alcohol stimulates the hypothalamic–pituitary–adrenal (HPA) axis. Part of this influence is likely exerted directly at the level of the corticotropin-releasing factor (CRF) gene, but intermediates may also play a role. Here we review the effect of alcohol on this axis, provide new data on the effects of binge drinking during adolescence, and argue for a role of catecholaminergic circuits. Indeed, acute injection of this drug activates brain stem adrenergic and noradrenergic circuits, and their lesion, or blockade of α1 adrenergic receptors significantly blunts alcohol-induced ACTH release. As alcohol can influence the HPA axis even once discontinued, and alcohol consumption in young people is associated with increased adult drug abuse (a phenomenon possibly mediated by the HPA axis), we determined whether alcohol consumption during adolescence modified this axis. The number of CRF-immunoreactive (ir) cells/section was significantly decreased in the central nucleus of the amygdala of adolescent self-administering binge-drinking animals, compared to controls. When another group of adolescent binge-drinking rats was administered alcohol in adulthood, the number of colocalized c-fos-ir and PNMT-ir cells/brain stem section in the C3 area was significantly decreased, compared to controls. As the HPA axis response to alcohol is blunted in adult rats exposed to alcohol vapors during adolescence, a phenomenon which was not observed in our model of self-administration, it is possible that the blood alcohol levels achieved in various models play a role in the long-term consequences of exposure to alcohol early in life. Collectively, these results suggest an important role of brain catecholamines in modulating the short- and long-term consequences of alcohol administration.
Inhibitory effect of osthole on alcohol-induced fatty liver in mice
2009, Digestive and Liver Disease
Citation Excerpt :
Therefore, alcoholic fatty liver should be treated as an important liver disorder. Sensitization of Kupffer cells is a prominent event in the initiation of alcoholic liver disease [3]. Sensitized Kupffer cells are activated by endotoxin (lipopolysaccharide, LPS), leading to a rapid increase in intracellular calcium followed by releases of inflammatory mediators (e.g., cytokines and lipid metabolites [4]), and reactive oxygen species (ROS).
Alcohol is a major cause of fatty liver, the disease is a spectrum that is initiated with steatosis, and without therapy it is apt to develop inflammation, necrosis, fibrosis and finally cirrhosis. There are currently no ideal pharmacological reagents that can prevent or reverse this disease. Osthole is an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, a Chinese herbal medicine, which has been used in clinics for many years. It has many functions such as anti-inflammation, anti-osteoporosis and anti-tumor and so on, but there is no report about treatment of alcoholic fatty liver in mice.
To examine the inhibitory effect of osthole on alcohol-induced fatty liver in mice and to investigate the potential mechanisms.
A mouse model with alcoholic fatty liver was induced by orally feeding 52% erguotou wine by gavage when they were simultaneously treated with osthole 10, 20, 40 mg/kg for 4 weeks. Whereafter, the lipids in serum and hepatic tissue, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione hormone (GSH), tumor necrosis factor-α (TNF-α) in hepatic tissue, hepatic weight coefficient and its histological evaluation were measured.
After treatment with osthole, the levels of serum total cholesterol (TC), triglyceride (TG), coefficient of hepatic weight, and the hepatic tissue contents of TC and TG were significantly decreased, the levels of MDA and TNF-α in liver were also decreased, while the GSH in liver was increased. Importantly, the histological evaluation of liver specimens demonstrated that osthole dramatically decreased lipid accumulation.
Osthole could inhibit alcohol-induced fatty liver in mice, and the mechanism might be associated with its anti-oxidation and suppression of TNF-α production.
Roles of Kupffer Cells in Alcoholic Liver Disease
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Oxidants and antioxidants in alcohol-induced liver disease
2003, Gastroenterology
Citation Excerpt :
There is accumulating evidence that inappropriate activation of Kupffer cells plays a key role in the initiation of alcohol-induced liver injury.38 Specifically, alcohol primes Kupffer cells and monocytes, increasing phagocytic and bactericidal activities, and cytokine production.39–41 Another major process that is stimulated in primed macrophages/monocytes is the production of prooxidants.
Although there are numerous experimental data indicating that oxidative stress plays a role in the initiation and progression of alcohol-induced liver disease (ALD), this work has yet to translate into an accepted antioxidant therapy for ALD in humans. With a better understanding of the mechanisms by which oxidative stress leads to liver damage during alcohol exposure, therapies that are more targeted at the cellular/molecular level may be applied in the clinic with potentially greater success. This article discusses the general concepts of oxidative stress and how it relates to current hypotheses in alcohol-induced liver injury, as well as lists several key questions that remain to be addressed in this field: (1) Which prooxidants are involved in ALD? (2) What are the sources of prooxidants in the liver during alcohol exposure? (3) How are oxidants involved in alcohol-induced liver injury? (4) Can a rational and effective antioxidant therapy against ALD be developed?
GASTROENTEROLOGY 2003;124:778-790

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Meeting reportEthanol and cytokine secretion

Abstract

J. Neuroimmunol.

Path. Res. Pract.

Gastroenterology

Life Sci.

Biochem. Biophys. Res. Commun.

Increased transforming growth factor β1 (TGF-β1) gene expression in human liver disease

Hepatology

Excessive in vitro bacterial lipopolysaccharide-induced production of monokines in cirrhosis

Hepatology

High interleukin 6 serum levels and increased production by leukocytes in alcoholic liver cirrhosis. Correlation with IgA serum levels and lymphokines production

Clin. Exp. Immunol.

Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1

J. Exp. Med.

Role of arachidonate metabolism in the immunoregulatory function of human leukocytic pyrogen/lymphocyte activating factor/interleukin 1

J. Immunol.