G. Szabo et al., Acute alcohol consumption attenuates interleukin-8 (IL-8) and monocyte chemoattractant peptide-1 (MCP-1) induction in response to ex vivo stimulation, J CLIN IMM, 19(1), 1999, pp. 67-76
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.