The modulation of B16BL6 melanoma metastasis is not directly mediated by cytolytic activity of natural killer cells in alcohol-consuming mice

Background: Previous studies in our laboratory indicate that alcohol consum ption suppresses the metastasis of B16BL6 melanoma, whereas the cytolytic a ctivity of natural killer (NK) cells is decreased in female C57BL/6 mice gi ven 20% w/v alcohol in their drinking water. In the present study, we furth er evaluated the involvement of NK cells and alcohol consumption in the cyt olytic activity of NK cells, the surface expression of NK phenotypic marker s, and metastasis of B16BL6 melanoma in C57BL/6 beige (bg(J)/bg(J)) mutant mice, which possess inherently low NK-cell cytolytic activity. Methods: Beige and control (bg(J)/+) mice were given either water or 20% w/ v of alcohol in drinking water for 61/2 to 7 weeks before assay for cytolyt ic activity, surface marker expression, and inoculation with B16BL6 melanom a intravenously or into the pinna of the ear. Results: NK cytolytic activity was suppressed in beige mice, and alcohol co nsumption did not modulate further the cytolytic activity. Beige mice had a lower percentage of NK cells in the peripheral blood and spleen than contr ol mice. Peripheral blood lymphocytes from beige mice also exhibited a redu ced percentage of CD4(+) T lymphocytes. Alcohol consumption similarly reduc ed the percentages of NK1.1- and LGL-I-expressing lymphocytes in the periph eral blood and spleen and reduced the percentage of CD8(+) T lymphocytes in the peripheral blood in both control and beige mice. Tumor lung colonizati on was increased in beige mice relative to control mice after intravenous i noculation of B16BL6 melanoma. The increase was more pronounced in water-dr inking beige mice than in control mice irrespective of alcohol consumption. Tumor lung colonization was significantly decreased (p < 0.05) by alcohol consumption in one experiment and partially decreased (p = 0.07) in the oth er. Mice that were inoculated into the pinna of the ear also exhibited a bl unted antimetastatic response to alcohol consumption. Conclusions: These data suggest that the presence of the beige mutation dim inishes the antimetastatic effect of alcohol consumption and that there is no interaction between alcohol consumption and NK-cell activity in the modu lation of lung metastasis of B16BL6 melanoma cells.