Acute alcohol intoxication suppresses the CXC chemokine response during endotoxemia.

BACKGROUND: CXC chemokines play an important role in host defense against infections. Alcohol is a frequently abused drug that inhibits numerous immune functions of the host. This study investigated the effects of alcohol on CXC chemokine macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC) responses in rats challenged with intravenous lipopolysaccharide (LPS).
METHODS: Acute ethanol intoxication was induced by an intraperitoneal injection of 20% alcohol (5.5 g/kg). Thirty minutes thereafter, LPS (500 microg/kg) was administered intravenously. In another set of experiments, rats were intravenously administered an anti-tumor necrosis factor-alpha (TNFalpha) neutralizing antibody (10 mg per rat) 2 hr before the LPS challenge.
RESULTS: At 1 and 2 hr after the LPS challenge, MIP-2, CINC, and TNFalpha concentrations in the plasma were significantly increased. Alcohol intoxication suppressed the MIP-2, CINC, and TNFalpha responses in the bloodstream during endotoxemia. Alcohol also suppressed the increase in plasma chemotactic activity and polymorphonuclear leukocyte adhesion molecule expression in rats with endotoxemia. MIP-2 and CINC messenger RNA (mRNA) expression was significantly increased 1 hr after endotoxemia in the lung, liver, and spleen. Alcohol suppressed the up-regulation of MIP-2 mRNA expression in all of these organs and CINC mRNA expression in the lungs of rats with endotoxemia. TNFalpha neutralization minimally inhibited plasma CINC and MIP-2 responses during endotoxemia and did not suppress the increase in plasma chemotactic activity.
CONCLUSIONS: These results show that alcohol suppresses the systemic CXC chemokine response to LPS, which is not primarily mediated by ethanol-induced suppression of TNFalpha. This disruption of host-defense function may serve as one mechanism underlying the increased risk of infectious diseases in hosts who abuse alcohol.