Selective inhibition of antigen-specific T lymphocyte proliferation by acute ethanol exposure: The role of impaired monocyte antigen presentation capacity and mediator production

G. Szabo, B. Verma, D. Catalano

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

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 (mφs) rather than on T cells. The immunodepressive effects of ethanol on mφ 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, FcγRI-negative (-31 ± 17%), and low-antigen-presenting, FcγRI-positive (-42 ± 15%) mφ subpopulations. Further analysis demonstrated that ethanol inhibits the production of interleukin-1β (IL-1β) and induces transforming growth factor β (TGF-β) 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-1β protein as well as IL-1β mRNA levels induced by adherence or bacterial stimulation. The causal relationship between decreased mφ IL-1β production, elevated TGF-β levels, and the decreased mφ APC capacity was further substantiated when exogenous IL-1β protein or anti-TGF-β 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 mφ APCs is not mediated by enhanced PGE2 production.

Original languageEnglish
Pages (from-to)534-544
Number of pages11
JournalJournal of Leukocyte Biology
Volume54
Issue number6
DOIs
Publication statusPublished - Jan 1 1993

Keywords

  • FcγRI (CD64)
  • concanavalin A
  • interleukin-1β
  • phytohemagglutinin
  • prostaglandin E
  • transforming growth factor α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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