Selective inhibition of antigen-specific T lymphocyte proliferation by acute ethanol exposure: the role of impaired monocyte antigen presentation capacity and mediator production.
Ethanol consumption is associated with impaired immunity. Our data demonstrate that even a single dose of a biologically relevant concentration (25-150 mM) of ethanol can down-regulate antigen-specific T lymphocyte proliferation. In contrast, ethanol augmented mitogen-induced T cell proliferation, suggesting that its inhibitory effect on antigen-specific T cell proliferation was due to its effects on monocytes (m phi s) rather than on T cells. The immunodepressive effects of ethanol on m phi antigen-presenting cell (APC) capacity were manifested whether alcohol treatment was limited to the antigen uptake-processing period only or was present during the entire period of antigen presentation. These inhibitory effects of ethanol were also evident on both the high-antigen-presenting, Fc gamma RI-negative (-31 +/- 17%), and low-antigen-presenting, Fc gamma RI-positive (-42 +/- 15%) m phi subpopulations. Further analysis demonstrated that ethanol inhibits the production of interleukin-1 beta (IL-1 beta) and induces transforming growth factor beta (TGF-beta) and prostaglandin E2 (PGE2), monocyte-derived mediators that can affect T cell proliferation. Ethanol resulted in a dose-dependent down-regulation of secreted and cell-associated IL-1 beta protein as well as IL-1 beta mRNA levels induced by adherence or bacterial stimulation. The causal relationship between decreased m phi IL-1 beta production, elevated TGF-beta levels, and the decreased m phi APC capacity was further substantiated when exogenous IL-1 beta protein or anti-TGF-beta neutralizing antibody prevented the down-regulatory effect of ethanol on antigen-specific T cell proliferation. Utilizing a cyclooxygenase inhibitor, we also demonstrated that the ethanol-induced decrease in m phi APCs is not mediated by enhanced PGE2 production.
Szabo
G
G
Department of Surgery, University of Massachusetts Medical Center, Worcester 01655.
Verma
B
B
Catalano
D
D
D000328:Adult; D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication / Q000187:drug effects; D000939:Epitopes / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology*; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D000431:Ethanol