title: Chronic ethanol consumption induces the production of tumor necrosis factor-alpha and related cytokines in liver and adipose tissue.
abstract: Increases in monocyte/macrophage production of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), parallel the evolution of liver injury in rats and humans with alcoholic liver disease. However, the possibility that TNF-alpha expression may be induced in other cell populations before serious liver disease develops has not been evaluated. To clarify this issue, mRNAs and/or protein levels of TNF-alpha and cytokines [interleukin (IL)-6, IL-10, transforming growth factor-beta (TGF)-beta, IL-12, and interferon-gamma] that regulate its biological activity were measured in sera, liver, and adipose tissues of rats that had developed hepatic steatosis after consuming ethanol-containing diets for 6 weeks. Cytokine expression in the ethanol-fed groups was compared with that of pair-fed controls rats that had received isocaloric amounts of a similar, ethanol-free diet for the same time period. Animals were studied both before and after a surgical stress (partial hepatectomy) that is known to provoke cytokine production. Chronic ethanol consumption led to increased serum concentrations of TNF and related cytokines, at least in part, by inducing the overproduction of these factors in the liver and peripheral adipose tissues. Despite the pair-feeding protocol that ensured similar calorie consumption in both groups, adipose tissues in ethanol-fed rats also expressed more leptin, a TNF-alpha-inducible mRNA that encodes an appetite-suppressing hormone. Thus, white adipose tissue can be an important source of cytokines in nonobese animals and may be a target for ethanol's actions. These data implicate TNF-alpha as a potential mediator of the nutritional-metabolic aberrations that often accompany chronic alcohol intake, even in the absence of advanced liver disease.
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: H Z
authors.initials: HZ
authors.lastname: Lin
authors.forename: S Q
authors.initials: SQ
authors.lastname: Yang
authors.forename: G
authors.initials: G
authors.lastname: Zeldin
authors.forename: A M
authors.initials: AM
authors.lastname: Diehl
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D000437:Alcoholism / Q000276:immunology* / Q000473:pathology; D000818:Animals; D016207:Cytokines / Q000097:blood*; D000431:Ethanol / Q000633:toxicity; D005235:Fatty Liver, Alcoholic / Q000276:immunology / Q000473:pathology; D020738:Leptin; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016207:Cytokines; D020738:Leptin; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol