Alcohol-mediated polarization of type 1 and type 2 immune responses.

Immune responses of alcoholics are often compromised, placing them at increased risk for frequent and severe infections. We demonstrate, using a murine model that parallels human alcoholism, that ethanol consumption polarizes adaptive immune responses by CD4+ T helper lymphocytes (Th). Alcohol impairs Th1-regulated cell-mediated, although Th2-regulated humoral responses are largely unimpaired and may be enhanced. Ethanol's effect is most pronounced during the early or cognitive phase of the immune response, when antigen-presenting cells (APC) interact with T cells. We find that alcohol does not act directly upon T cells, but upon APC. Consequences of this interaction of alcohol with APC in vivo are diminished Th1-mediated delayed hypersensitivity (DTH) reactions, while at the same time increased Th2-regulated serum IgE levels are seen. Further ethanol consumption leads to decrease affinity of the IgG2a and IgG2b Th1-regulated antibody isotypes.