title: Ethanol affects release of TNF and GM-CSF and membrane expression of TNF receptors by human macrophages.
abstract: Ethanol intoxication has been associated with bacterial pneumonia and tuberculosis. More recently, ethanol was shown to impair the capacity of pulmonary macrophages to produce superoxide anion and tumor necrosis factor (TNF). Furthermore, exposure to ethanol compromises macrophage's ability to respond to stimulation with TNF and granulocyte-macrophage colony-stimulating factor (GM-CSF), and kill an intracellular pathogen, Mycobacterium avium. Based on these previous findings, we examined whether exposure to ethanol affects superoxide anion production, synthesis of cytokines, and expression of membrane receptors to TNF on human monocyte-derived macrophages. Brief exposure to 10 or 50 micrograms/dl of ethanol significantly reduced the macrophage's response to a subsequent stimulus with phorbol ester (phorbol-12-myristate-13-acetate, PMA), and this unresponsive state lasts for approximately 6 h following removal of ethanol. When macrophages were then treated with lipopolysaccharide (LPS) in the presence of ethanol, high concentrations of TNF and GM-CSF were produced, but subsequent stimulation with LPS (second stimulus) was associated with significant impairment on synthesis and release of both TNF and GM-CSF. In addition, although ethanol had no effect on TNF binding to resting macrophages and to macrophages infected with M. avium, ethanol significantly reduced the expression of TNF receptors on interferon-gamma-stimulated macrophages. The ethanol-induced inhibition of macrophage function suggests potential mechanisms for suppression of the host's immune response and consequently increased susceptibility for infectious diseases.
authors.affiliation: Kuzell Institute for Arthritis and Infectious Diseases, Pacific Presbyterian Medical Center, CA 94115.
authors.forename: L E
authors.initials: LE
authors.lastname: Bermudez
authors.forename: M
authors.initials: M
authors.lastname: Wu
authors.forename: J
authors.initials: J
authors.lastname: Martinelli
authors.forename: L S
authors.initials: LS
authors.lastname: Young
mesh_terms: D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D000431:Ethanol / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009164:Mycobacterium Infections / Q000276:immunology*; D009162:Mycobacterium avium / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D000431:Ethanol; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor