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

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 re sult 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 vivo acute alcohol treatment of normal bloo d monocytes resulted in a significant, dose-dependent (25-100 mM) attenuati on of staphylococcus enterotoxin B (SEB), phytohemagglutinin (PHA), or IFN gamma-induced monocyte IL-8 and MCP-1 production (P < 0.01). Likewise, etha nol (100 mM) irt vitro reduced MCP-1 levels in response to SEE, PHA, or IFN gamma stimulation in mononuclear cells (31-62% reduction). Furthermore, ac ute alcohol consumption (0.85 g/kg body weight) significantly attenuated SE B- or LPS-induced IL-8 and MCP-1 levels in whole-blood samples obtained 4 h r after alcohol consumption from normal nonalcoholic individuals (P < 0.01) . RANTES and MIP-1 beta were only minimally inhibited (16-25% inhibition) b y in vitro ethanol (100 mM) in mononuclear cells, suggesting that ethanol m ay have a selective effect on the regulation of various chemokines. These r esults demonstrate that acute alcohol, in vivo as well as in vitro, attenua tes monocyte-derived chemokine production in response to a subsequent immun e challenge. Our data show for the first time that activation of nuclear re gulatory factor kappa B (NF-kappa B), a common regulator binding in the pro moter region of IL-8 and MCP-1 genes, is inhibited by acute ethanol (25 mM) treatment in SEE-stimulated human monocytes. These results imply that inhi bition of NF-kappa B activation may be one of the intracellular mechanisms for the ethanol-induced inhibition of IL-8 and MCP-1 production in monocyte s. 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 progres sion of the disease.