Immune Responses to Ethanol Metabolites and Cytokine Profiles Differentiate Alcoholics with or without Liver Disease.

Department of Laboratory Medicine and Addiction Research Unit, EP Central Hospital, Seinäjoki, and University of Tampere, Finland.
The American Journal of Gastroenterology (Impact Factor: 9.21). 07/2005; 100(6):1303-10. DOI: 10.1111/j.1572-0241.2005.41509.x
Source: PubMed

ABSTRACT Excessive alcohol consumption is associated with the generation of antibodies against neoantigens induced by ethanol metabolism. However, the associations between such immune responses, ethanol consumption, and liver injury remain unclear.
Eight-six male alcoholics with (n=54) or without (n=32) liver disease, and 20 male volunteers (6 abstainers, 14 moderate drinkers) underwent clinical, morphological, and biochemical assessments of liver status and ethanol consumption.
Antiacetaldehyde adduct IgAs in both groups of alcoholics were significantly higher than those in the controls. Elevated IgGs occurred in patients with liver disease, whereas IgMs were high in the heavy drinkers without apparent liver disease. Liver disease patients had high levels of both proinflammatory (IL-2, IL-6, IL-8, TNF-alpha) and antiinflammatory (IL-10) cytokines, whereas those without liver disease showed elevated IL-6, IL-8, and IL-10 only. Ethanol consumption correlated significantly with antiadduct IgA and IL-6 levels, which also showed parallel changes upon abstinence.
Alcoholic liver disease is associated with the generation of IgAs and IgGs against acetaldehyde-derived antigens and enhanced levels of both pro- and antiinflammatory cytokines, whereas elevated IgA, IL-6, and IL-10 characterize alcoholics without liver disease. These data suggest that immunological mechanisms may play a role in the sequence of events leading to liver disease in some patients with excessive drinking.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: High fat diet and chronic alcohol consumption cause hyperlipidemia, steatohepatitis and in some cases, cirrhosis. But the detailed mechanisms are not known. Scutellariae Radix (SR) has been known to have hepatoprotective effects. The aim of this study was, therefore, to determine whether SR water extract (100 mg/kg) could affect immune function in mice abused by long-term alcohol consumption (feed 25% ethanol in water for 1 month, ad libitum) with high fat diet (40% fat of total calorie). Mice received either a regular diet (RD, AIN 93) or a high fat diet (HD); high fat diet group were divided into ethanol group (HED) or ethanol with SR water extract group (HEDS). Food consumption was measured daily and body weights recorded weekly throughout the experiment. Immunological parameters (Ig A, Ig E, TNF-, IFN-, IL-) were measured from the serum and the supernatant of spleen lymphocytes from the all groups. The concentration of serum Ig A, Ig E and cytokines were significantly higher in the alcohol consumed groups. Also the concentration of supernatant of spleen lymphocytes, Ig A, Ig E, cytokines were significantly higher in the ethanol consumption groups. Otherwise, HEDS group were significantly lower than HED group. These results suggest that SR water extract may improve the haptic immune function in mice fed high fat diet with alcohol.
    Journal of the Korean Society of Food Science and Nutrition 01/2006; 35(5). DOI:10.3746/jkfn.2006.35.5.536
  • [Show abstract] [Hide abstract]
    ABSTRACT: Oyster extract is an effective bioactivity component. It has abundant nutritional value and antiviral, antitumor and immune defense functions. The role of oyster extract in treating liver injury has been paid more attention. We use Wistar rats to make alcoholic liver disease model through injecting alcohol into rats’ stomachs. These rats were randomly divided into five groups: model group, control group, low-dose, middle-dose and high-dose experimental group with a dose of 0.12 g kg−1, 0.40 g kg−1, and 1.20 g kg−1 alcoholic. After nine weeks, serum biomarkers (ALT, AST, TG and TCHO), malondialdehyde (MDA), glutathione (GSH), C3a, C5a, IL-17, TNF-α, anti-MAA-HAS IgG, CD3+, CD4+, CD8+, NK cell activation and zinc content were assessed. The results showed that the serum biomarkers(ALT, AST, TG and TCHO), MDA content, anti-MAA-HSA IgG, serum C3a, C5a IL-17 and TNF-α levels of oyster extract treatment groups were significantly decreased in comparison with model group. On the contrary, GSH showed adverse trend. Serum CD3+, CD4+ and NK cell activation were significantly increased in middle-dose group and high-dose group compared with model group, and there was decrease of CD8+ activity in high-dose group. Plasma Zn level was decreased in model group compared with that in control group. Meanwhile, Mean plasma Zn levels increased dramatically following the dose increase of a given oyster extract.
    Journal of Ocean University of China 03/2014; 13(2). DOI:10.1007/s11802-014-2449-0 · 0.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential.