Inhibition of superantigen-induced T cell proliferation and monocyte IL-1 beta, TNF-alpha, and IL-6 production by acute ethanol treatment.
Alcohol use has been shown to decrease monocyte antigen presentation capacity and inflammatory cytokine production, thereby increasing susceptibility to infections. Here, we demonstrate that in vitro acute treatment of normal monocytes with pharmacological doses of ethanol can decrease superantigen [Staphylococcus enterotoxins B (SEB) and A (SEA)]-induced T cell proliferation. Furthermore, ethanol treatment (25-100 mM) significantly inhibited SEA- or SEB-induced production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 in monocytes. Ethanol-induced down-regulation of monocyte TNF-alpha, IL-1 beta, and IL-6 occurred at both the protein and mRNA levels. Additional data suggest that ethanol can decrease IL-1 beta mRNA stability. Furthermore, experiments using cycloheximide indicate that de novo protein synthesis is required for the inhibitory effect of ethanol on SEB-induced IL-1 beta mRNA production. Finally, ethanol treatment decreased HLA-DR expression in monocytes, suggesting that ethanol treatment can compromise monocyte stimulation by down-regulating the SEB-binding capacity of monocytes. These results suggest that acute ethanol treatment can interfere with monocyte activation by SEB at multiple steps. Consequently, decreased superantigen-induced polyclonal T cell activation and inflammatory monokine production would contribute to an impaired immune response to bacterial challenge with superantigens after acute alcohol intake.
Szabo
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Department of Surgery, University of Massachusetts Medical Center, Worcester 01655, USA.
Mandrekar
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Catalano
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D000328:Adult; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D007375:Interleukin-1; D015850:Interleukin-6; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol