A Dynamic Flux in Natural Killer Cell Subsets as a Function of the Duration of Alcohol Ingestion

Background: Chronic ethanol (EtOH) consumption is associated with a wide variety of immune abnormalities including changes in T cells, B cells, dendritic cells, and natural killer (NK) cells. However, there is conflicting information as to the direction of such immune changes. The hypothesis that was tested in this report is that, for NK cells, the changes can vary as a function of the duration of alcohol ingestion. Methods: Using the MeadowsCook murine model of chronic alcohol ingestion, the changes in NK cell function and subset distribution were examined as a function of the duration of alcohol ingestion. Results: Acute alcohol ingestion resulted in decreased number and cytotoxic function of NK cells with no effect on intracellular interferon gamma expression. These abnormalities normalized after 12 to 14 days of alcohol ingestion and there was an increase of NK cell number and cytotoxicity after 8 weeks of continued EtOH ingestion. Ten weeks of continued alcohol consumption results in a significant decrease in the Ly49H+ CD11b+ CD27- splenic NK cell subset; this difference continued to be significant at 30 weeks. Conclusions: This report may explain some of the conflicting data in the literature that examined NK cell activity in alcoholic patients. It is apparent that various abnormalities can be seen in NK cell activity and subset distribution with the flux being a function of the duration of alcohol ingestion. The demonstration of a decrease in the Ly49H+ subset (which is known to be involved in resisting murine cytomegalovirus infection) may explain the reported increase in susceptibility to some viral infections in chronic alcohol abuse. Another novel finding is that changes of some subsets of NK cells are not evident until at least 10 weeks of continued EtOH consumption.