Ethanol decreases host resistance to pulmonary metastases in a mouse model: role of natural killer cells and the ethanol-induced stress response.
The present study was done to delineate cause-effect relationships between the ethanol (EtOH)-induced stress response, natural-killer (NK)-cell activity, and resistance to experimental metastases of B16F10 melanoma cells in mice. Increased numbers of metastatic nodules were noted in the lungs of mice treated with dosages of EtOH that produce peak blood levels of 0.25-0.4%. EtOH caused only a minor depletion of NK cells or NK-cell activity from the spleen or lungs of normal or B16F10-challenged mice. However, in earlier studies we have shown consistent, significant decreases in NK-cell activity (approx. 50%) in spleen preparations from EtOH-treated mice. Depletion of NK cells by a monoclonal antibody increased the number of B16F10 nodules in the lungs, confirming an important role for NK cells for resistance to B16F10 metastases. Treatment of NK-cell-depleted mice with EtOH caused no further decrease in resistance to B16F10 cells, indicating that suppression of NK-cell activity is the major mechanism by which EtOH suppresses resistance to B16F10 metastases. Adrenalectomy or a glucocorticoid antagonist partially prevented EtOH-induced increases in the number of metastatic nodules in the lungs. Administration of exogenous corticosterone increased the number of B16F10 nodules to an extent similar to that caused by EtOH. These results indicate a role for the EtOH-induced stress response in decreasing resistance to B16F10 metastases. EtOH-induced decreases in resistance to cancer have also been reported in rats. The findings of the present study support the possibility that this is a generalized phenomenon, which could occur in humans.
Wu
W J
WJ
Department of Cellular Biology and Anatomy, Louisiana State University Medical Center, Shreveport, LA, USA.
Pruett
S B
SB
D000315:Adrenalectomy; D000428:Alcohol Drinking / Q000276:immunology*; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008168:Lung / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000556:secondary*; D008546:Melanoma, Experimental / Q000276:immunology* / Q000556:secondary*; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D013154:Spleen / Q000276:immunology; D013312:Stress, Physiological / Q000276:immunology / Q000503:physiopathology*
D000431:Ethanol