Mechanisms of suppression of poly I:C-induced activation of NK cells by ethanol

We have previously reported that ethanol (EtOH) decreases polyinosinic–polycytidylic acid (poly I:C) and interleukin-2 (IL-2)-induced upregulation of natural killer (NK) cell lytic activity in mice. The present study was designed to determine if decreased production of or response to interferon-α (IFN-α) is involved and if this is associated with inhibited upregulation of perforin or granzyme B. Treatment of mice with poly I:C upregulated IFN-α and granzyme B, but not perforin, in the spleen. Administration of EtOH before poly I:C prevented the upregulation of IFN-α and granzyme B and decreased perforin levels. EtOH exposure in vivo rendered splenocytes less able to respond to IFN-α upon in vitro exposure to poly I:C. Exogenous IFN-α only partially prevented this decreased response. Thus, decreased production of and response to IFN-α as well as decreased levels of granzyme B and perforin are implicated in the diminished activation of NK cell lytic function in EtOH-treated mice.