title: Down-regulation of tumor necrosis factor alpha activity by acute ethanol treatment in human peripheral blood monocytes.
abstract: As the most commonly used drug that can modulate both metabolic and immune pathways, ethanol is evaluated in this report as a regulator of tumor necrosis factor alpha (TNF alpha) production in human peripheral blood monocytes (M phi) in combination with a variety of stimuli. While acute ethanol treatment did not induce TNF alpha in M phi, it was a potent down-regulator of M phi TNF alpha production whether induced by the combination of interferon-gamma plus muramyl dipeptide (MDP) (P < 0.001), lipopolysaccharide (LPS) alone (P < 0.01), or interferon-gamma plus LPS. Down-regulation of M phi TNF alpha by ethanol was dose dependent and statistically significant in the biologically relevant, 25-150 mM, ethanol concentration range. We also demonstrate that these ethanol concentrations did not affect M phi viability. TNF alpha down-regulation by ethanol was most effective when ethanol was administered 4 hr prior to MDP stimulation; however, it was also effective--though to a lesser extent--if it was added at the time of MDP stimulation. Furthermore, ethanol also down-regulated TNF alpha production of the in vivo preactivated M phi of trauma patients, which produce hyperelevated levels of TNF alpha. We have previously shown that the majority of posttrauma elevated M phi TNF alpha is produced by the M phi subpopulation expressing high-affinity type I Fc gamma receptors (Fc gamma RI). When the Fc gamma RI cross-linking-stimulated M phi subpopulation was treated with acute ethanol, TNF alpha production was suppressed again both in in vivo preactivated M phi of trauma patients and in M phi of normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Surgery, University of Massachusetts Medical Center, Worcester 01655.
authors.forename: B K
authors.initials: BK
authors.lastname: Verma
authors.forename: M
authors.initials: M
authors.lastname: Fogarasi
authors.forename: G
authors.initials: G
authors.lastname: Szabo
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D002448:Cell Adhesion; D002469:Cell Separation; D002470:Cell Survival; D015232:Dinoprostone / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D000431:Ethanol / Q000032:analysis / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D017452:Receptors, IgG / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
chemical_list: D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma; D015232:Dinoprostone; D007213:Indomethacin