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.
Department of Pharmacology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Omar
O
Latif
Jeffrey D
JD
Peterson
Carl
C
Waltenbaugh
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000097:blood; D000918:Antibody Specificity / Q000187:drug effects; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D003619:Dansyl Compounds / Q000138:chemical synthesis / Q000378:metabolism; D004032:Diet; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000097:blood / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D005719:gamma-Globulins / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D003619:Dansyl Compounds; D005719:gamma-Globulins; D000431:Ethanol; D010047:Ovalbumin; C029038:dansyl chloride