The effect of ethanol consumption in C57BL/6 mice on natural killer cell proliferation and development

Natural killer (NK) cells are important immune cells capable of recognizing and eliminating pathogen-infected cells and tumor cells without the need for prior activation or immunization. Previous studies in our laboratory showed that proliferation stimulated by interleukin (IL)-2 in vitro is suppressed in NK cells from C57BL/6 mice drinking 20% (w/v) ethanol for two weeks. In this study we administered exogenous rhIL-2 twice-daily for 3 days to determine the effect of alcohol consumption on NK proliferation in vivo. Intraperitoneal administration of rhIL-2 significantly increased the number of splenic NK cells in both water-drinking mice and in mice drinking 20% ethanol for two weeks. In water-drinking mice, the maximum increase in NK cell number was 2.4-fold after administration of 30,000 IU rhIL-2 per injection while in alcohol-drinking mice, the splenic NK cell number increased 3.3-fold. These data suggest that NK cells in alcohol-drinking mice are more responsive to the IL-2 proliferative stimulus in vivo than NK cells in water-drinking mice. The development of NK cells is dependent on IL-15, whose receptor is comprised of the IL-2 receptor (IL-2R)β and IL-2Rγ subunits. By flow cytometry we examined the effect of alcohol consumption on the maturation phenotype of NK cells in the bone marrow, as well as the liver and spleen. In the spleen and liver, but not in the bone marrow, the fraction of NK cells expressing the more mature phenotype of NK1.1 +CD3−Mac-1+ was higher in water-drinking mice compared to alcohol-drinking mice. These data suggest that alcohol consumption reduces the population of mature NK cells in the spleen and liver. During the development of NK cells there is a phase of expansion before the acquisition of Mac-1. Thus, we suggest that the increased responsiveness of NK cells from alcohol-drinking mice to proliferative stimuli results in a selective expansion of immature NK cells, resulting in an increased ratio of Mac-1− to Mac-1+ NK cells. The ability of alcohol consumption to delay or inhibit NK maturation could be responsible for the increased severity and susceptibility of alcoholics to viral infections, against which NK cells provide important immune defense.