Molecular mechanisms of the dose-dependent effects of alcohol on the immune system and HPA regulation remain poorly understood due to a lack of systematic studies that examine the effect of multiple doses and different time courses. There may be important differences in the effects of ethanol on the immune system depending on whether the study is conducted in vitro or in vivo, as the latter allows for a complex psychogenic component in which stress-related hormones and immune-signaling molecules interact. In addition, most studies have been done in vitro using primary cells or cell lines in the presence of rather high, constant doses of ethanol. Similarly, most rodent studies to date have focused on acute/short-term binge models utilizing high concentration of ethanol (20% ethanol) as the sole source of fluid, a possible stressor in itself. Therefore, there is a pressing need for in depth studies that examine dose-dependent effects of chronic ethanol consumption on immunity in vivo to allow for the complex interactions between ethanol, its metabolites, HPA signaling, nutritional deficiencies, and the immune system.
