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Down-regulation of tumor necrosis factor α activity by acute ethanol treatment in human peripheral blood monocytes

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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 α (TNFα) production in human peripheral blood monocytes (Mφ) in combination with a variety of stimuli. While acute ethanol treatment did not induce TNFα in Mφ, it was a potent down-regulator of Mφ TNFα production whether induced by the combination of interferon-γ plus muramyl dipeptide (MDP) (P<0.001), lipopolysaccharide (LPS) alone (P<0.01), or interferon-γ plus LPS. Down-regulation of Mφ TNFα 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 Mφ viability. TNFα 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 TNFα production of thein vivo preactivated Mφ of trauma patients, which produce hyperelevated levels of TNFα. We have previously shown that the majority of posttrauma elevated Mφ TNFα is produced by the Mφ subpopulation expressing high-affinity type I Fcγ receptors (FcγRI). When the FcγRI cross-linking-stimulated Mφ subpopulation was treated with acute ethanol, TNFα production was suppressed again both inin vivo preactivated Mφ of trauma patients and in Mφ of normal controls. In experiments utilizing cyclooxygenase inhibitor, we also demonstrate that ethanol has a direct, prostaglandin E2-independent, effect on Mφ TNFα production. These results demonstrate that acute ethanol exposure has the potential to down-regulate Mφ production of TNFα significantly regardless of the TNFα-inducing stimulus. Decreased capacity of Mφ to produce TNFα might, therefore, contribute to the immunological and metabolic abnormalities described after ethanol uptake.

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  1. Department of Surgery, University of Massachusetts Medical Center, 55 Lake Avenue North, 01655, Worcester, Massachusetts

    Bikash K. Verma, Miklos Fogarasi & Gyongyi Szabo

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Verma, B.K., Fogarasi, M. & Szabo, G. Down-regulation of tumor necrosis factor α activity by acute ethanol treatment in human peripheral blood monocytes. J Clin Immunol 13, 8–22 (1993). https://doi.org/10.1007/BF00920631

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