Acute alcohol consumption attenuates interleukin-8 (IL-8) and monocyte chemoattractant peptide-1 (MCP-1) induction in response to ex vivo stimulation.

Abstract

Chronic alcohol use is associated with impaired immunity and host defense. Even acute ethanol treatment both in vitro and in vivo has been shown to result in decreased inflammatory cytokine production. However, the potential immunoregulatory effects of acute, moderate alcohol use are yet to be fully explored. Here we show that in vitro acute alcohol treatment of normal blood monocytes resulted in a significant, dose-dependent (25–100 mM) attenuation of staphylococcus enterotoxin B (SEB), phytohemagglutinin (PHA), or IFNγ-induced monocyte IL-8 and MCP-1 production (P < 0.01). Likewise, ethanol (100 mM) in vitro reduced MCP-1 levels in response to SEB, PHA, or IFNγ stimulation in mononuclear cells (31–62% reduction). Furthermore, acute alcohol consumption (0.85 g/kg body weight) significantly attenuated SEB- or LPS-induced IL-8 and MCP-1 levels in whole-blood samples obtained 4 hr after alcohol consumption from normal nonalcoholic individuals (P < 0.01). RANTES and MIP-1β were only minimally inhibited (16–25% inhibition) by in vitro ethanol (100 mM) in mononuclear cells, suggesting that ethanol may have a selective effect on the regulation of various chemokines. These results demonstrate that acute alcohol, in vivo as well as in vitro, attenuates monocyte-derived chemokine production in response to a subsequent immune challenge. Our data show for the first time that activation of nuclear regulatory factor κB (NF-κB), a common regulator binding in the promoter region of IL-8 and MCP-1 genes, is inhibited by acute ethanol (25 mM) treatment in SEB-stimulated human monocytes. These results imply that inhibition of NF-κB activation may be one of the intracellular mechanisms for the ethanol-induced inhibition of IL-8 and MCP-1 production in monocytes. Thus, impaired chemokine (particularly MCP-1 and IL-8) induction upon an immune challenge is likely to contribute to compromised host defense after acute alcohol consumption and may also affect progression of diseases such as atherosclerosis or HIV infection where chemokines contribute to progression of the disease.