title: IFN-γ is essential for the inhibition of B16BL6 melanoma lung metastasis in chronic alcohol drinking mice.
abstract: We previously found that chronic alcohol consumption (20% w/v in drinking water) that models the level consumed by human alcoholics, when administered to female C57BL/6 mice inhibits B16BL6 melanoma metastasis to the lung; however, the mechanism is not known. Chronic alcohol consumption increases IFN-γ producing NK, NKT, CD4(+), and CD8(+) T cells. To examine the impact of IFN-γ on metastasis, we inoculated B16BL6 melanoma cells i.v. into control and chronic alcohol drinking IFN-γ knockout (KO) mice. Knockout of the ifn-γ gene abrogated the anti-metastatic effects associated with alcohol consumption. We examined metastasis in common gamma-chain (γC) KO mice, which are deficient in NK, NKT and CD8(+) T cells, and in Vα14Jα281(-/-) KO mice, which are deficient in invariant NKT (iNKT) cells, in order to assess the importance of specific IFN-γ producing cell types to this effect. We found that the antimetastatic effect of alcohol was still present in γC KO mice and also in γC KO mice depleted of Gr-1(+) cells. Knockout of iNKT cells reduced the degree but not the antimetastatic effect associated with alcohol. These results indicate that the antimetastatic effect induced by chronic alcohol consumption is IFN-γ dependent and that multiple IFN-γ producing cell types contribute to this effect.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA 99164-6534, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Zhu
authors.forename: Jenifer M
authors.initials: JM
authors.lastname: McKinley
authors.forename: Gary G
authors.initials: GG
authors.lastname: Meadows
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000437:Alcoholism / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D007371:Interferon-gamma