Ethanol augments intracellular survival of Mycobacterium avium complex and impairs macrophage responses to cytokines.
Chronic ethanol ingestion predisposes to tuberculosis and bacterial pneumonia. Mycobacterium avium complex (MAC) organisms cause bacteremia in patients with AIDS. Cultured human monocyte-derived macrophages and murine Kupffer cells were exposed to 10-100 micrograms/dl ethanol; significantly greater intracellular growth of MAC strains 100 (serovar 8) and 101 (serovar 1) occurred in ethanol-treated cells than in controls (range, 58% +/- 7%-70% +/- 5%; P less than .05 for 50 and 100 micrograms/dl ethanol vs. control). Both cell types, when treated with 10(3) units/ml recombinant tumor necrosis factor (TNF) or 10(2) units/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) in the presence of 10-100 micrograms/dl ethanol, killed significantly fewer MAC than controls (49% +/- 12% decrease for GM-CSF and 57% +/- 16% for TNF; P less than .05 for all comparisons). C57BL black mice infected intravenously with MAC strain 101 were given ethanol as 4% of total calories daily; after 21 days they had greater numbers of MAC in blood, liver, and spleen than controls. Ethanol's effects on the interaction between the host and MAC favor progressive infection.
Bermudez
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Kuzell Institute for Arthritis and Infectious Diseases, San Francisco, CA 94115.
Young
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D000437:Alcoholism / Q000150:complications; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007728:Kupffer Cells / Q000187:drug effects / Q000382:microbiology; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015269:Mycobacterium avium Complex / Q000187:drug effects* / Q000254:growth & development; D015270:Mycobacterium avium-intracellulare Infection / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D016178:Granulocyte-Macrophage Colony-Stimulating Factor