Ethanol suppresses polyinosinic:polycytidylic acid-induced activation of natural killer cells primarily by acting on natural killer cells, not through effects on other cell types.

Natural killer (NK) cells can be activated in vitro and in vivo by polyinosinic:polycytidylic acid (poly I:C) through induction of type I interferons or other cytokines. Ethanol suppresses in vivo and ex vivo poly I:C activation of NK cell activity in a mouse model for binge drinking, but it is not known whether this effect is mediated by changes in NK cells or in other cell types (e.g., those that produce NK cell-activating cytokines). Splenocytes were obtained from C57BL/6 [NK cell-competent (NKc)] and C57BL/6 perforin knockout [NK cell-incompetent (NKi)] mice 6 h after administration of ethanol (6 g/kg) or vehicle (VH; dH(2)O). Cells were incubated in vitro 18 h with poly I:C (100 micro g/ml), followed by a 4-h 51Cr release assay with the use of YAC-1 target cells. Results of cell-mixing experiments involving all relevant combinations of splenocytes obtained from NKc and NKi mice treated with VH or ethanol strongly supported the suggestion that NK cells, not other cell types, are the primary target of ethanol-induced suppression of NK cell activation. For example, mixing of splenocytes obtained from ethanol-treated NKc and VH-treated NKi mice or from ethanol-treated NKc and ethanol-treated NKi mice yielded similar cytolytic function. However, mixing of splenocytes obtained from ethanol-treated NKc and VH-treated NKi mice yielded significantly less cytolytic activity than that of splenocytes from VH-treated NKc and ethanol-treated NKi mice. In addition, mixing of splenocytes obtained from VH-treated NKc and NKi mice resulted in lower cytolytic activity than when splenocytes from the NKi mice were treated with ethanol instead of with VH, demonstrating that ethanol did not decrease the function of other cell types. A strikingly similar pattern of results was observed when B6C3F1 mice, rendered NK cell deficient by administration of anti-NK 1.1 monoclonal antibody, were used instead of perforin knockout mice. These results indicate that ethanol suppresses activation of NK cells primarily by suppressing the NK cell response to poly I:C, not by acting on another cell type.