Immune dysfunction is common to both the alcoholic and AIDS patient, and one deficiency shared by these two groups is a decrease in natural killer (NK) cell activity that is an important host defense mechanism against certain infections and neoplastic diseases. While some studies show that NK cell activity is decreased by alcohol, other studies have reported no change or even increased NK cell activity. Interpretation of these studies is difficult because NK cell activity can be influenced by nutritional and liver status and the nature of the experimental conditions. The effect of alcohol on NK cell function is unclear. Our preliminary data indicate that chronic high alcohol consumption decreases pooled splenic NK cell activity. Thus, our objective is to confirm our preliminary findings in individual mice and to determine the dose level, and duration of feeding required to induce a decrease in NK cell activity. We will correlate these effects with blood alcohol level in mice chronically fed three dose levels of alcohol and solid diet that maintains nutritional status. We will also assess the effect of alcohol on experimental and spontaneous metastasis of B16-bladder 6 melanoma, a highly invasive and metastatic cell line, to determine the biological significance of alcohol-induced decrease in NK cell activity. Lastly, we will undertake studies to identify the mechanism underlying alcohol's effect on NK cell activity. We will conduct experiments to determine if a) effector target binding is altered, b) suppressor factors are involved in inhibiting NK cell activity, and c) examine whether alcohol decreases the number of NK cells. To do the latter, we will quantify and sort NK cell populations using fluorescence activated cell sorting based on the expression of asialo-GM1 and NK-1 surface markers. In correlating the effect that alcohol has on NK cells with the effects reported in the AIDS patient, our investigation may implicate alcohol as a potential risk for increasing susceptibility to Kaposi's sarcoma and other neoplastic diseases in the AIDS patient and in the alcohol abuser to developing AIDS and cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA007293-02
Application #
3111055
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1987-07-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Washington State University
Department
Type
Schools of Pharmacy
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164
Meadows, Gary G (2012) Diet, nutrients, phytochemicals, and cancer metastasis suppressor genes. Cancer Metastasis Rev 31:441-54
Zhang, Hui; Zhu, Zhaohui; Meadows, Gary G (2012) Chronic alcohol consumption impairs distribution and compromises circulation of B cells in B16BL6 melanoma-bearing mice. J Immunol 189:1340-8
Vorderstrasse, Beth A; Wang, Tao; Myers, Annette K et al. (2012) Alcohol consumption suppresses mammary tumor metastasis in a syngeneic tumor transplantation model. Breast Cancer Res Treat 136:729-37
Powers, John; Zhang, Hui; Battrell, Logan et al. (2012) Establishment of an immunodeficient alcohol mouse model to study the effects of alcohol on human cells in vivo. J Stud Alcohol Drugs 73:933-7
Zhang, Xingqi; Lan, Ni; Bach, Paxton et al. (2012) Prenatal alcohol exposure alters the course and severity of adjuvant-induced arthritis in female rats. Brain Behav Immun 26:439-50
Wang, Tao; Wyrick, Katie L; Meadows, Gary G et al. (2011) Activation of the aryl hydrocarbon receptor by TCDD inhibits mammary tumor metastasis in a syngeneic mouse model of breast cancer. Toxicol Sci 124:291-8
Zhang, Hui; Zhu, Zhaohui; Meadows, Gary G (2011) Chronic alcohol consumption decreases the percentage and number of NK cells in the peripheral lymph nodes and exacerbates B16BL6 melanoma metastasis into the draining lymph nodes. Cell Immunol 266:172-9
Zhang, Hui; Zhu, Zhaohui; McKinley, Jenifer M et al. (2011) IFN-? is essential for the inhibition of B16BL6 melanoma lung metastasis in chronic alcohol drinking mice. Clin Exp Metastasis 28:301-7
D'Souza El-Guindy, Nympha B; Kovacs, Elizabeth J; De Witte, Philippe et al. (2010) Laboratory models available to study alcohol-induced organ damage and immune variations: choosing the appropriate model. Alcohol Clin Exp Res 34:1489-511
Zhang, Hui; Meadows, Gary G (2010) Chronic alcohol consumption enhances myeloid-derived suppressor cells in B16BL6 melanoma-bearing mice. Cancer Immunol Immunother 59:1151-9

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