Acute alcohol intoxication suppresses the CXC chemokine response during endotoxemia

Alcohol Clin Exp Res. 2002 Jan;26(1):65-73.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alcoholic Intoxication / immunology*
  • Animals
  • Antibody Specificity
  • Chemokine CXCL1
  • Chemokine CXCL2
  • Chemokines / biosynthesis
  • Chemokines / blood
  • Chemokines / genetics
  • Chemokines, CXC / antagonists & inhibitors*
  • Chemokines, CXC / biosynthesis
  • Chemotactic Factors / biosynthesis
  • Chemotactic Factors / blood
  • Endotoxemia / immunology*
  • Endotoxemia / metabolism
  • Epitopes / immunology
  • Growth Substances / biosynthesis
  • Growth Substances / blood
  • Immunosuppressive Agents / blood*
  • Immunosuppressive Agents / toxicity
  • Intercellular Signaling Peptides and Proteins*
  • Male
  • RNA, Messenger / biosynthesis
  • Rats
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Chemokine CXCL1
  • Chemokine CXCL2
  • Chemokines
  • Chemokines, CXC
  • Chemotactic Factors
  • Cxcl1 protein, mouse
  • Cxcl1 protein, rat
  • Cxcl2 protein, mouse
  • Cxcl2 protein, rat
  • Epitopes
  • Growth Substances
  • Immunosuppressive Agents
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha