Acute ethanol intoxication suppresses lung chemokine production following infection with Streptococcus pneumoniae.
Alcohol intoxication impairs neutrophil function and increases host susceptibility to Streptococcus pneumoniae. In a rat model of pneumonia, the effects of acute intoxication were monitored for lung chemokine responses, neutrophil recruitment, and bactericidal activity. Alcohol delayed lung neutrophil recruitment, increased bacterial burden, and decreased survival. Before neutrophil recruitment, bronchoalveolar lavage (BAL) macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC) were decreased by alcohol. This alcohol-induced effect was reversed at 6 h, when there were large numbers of neutrophils in control BAL fluid, compared with the alcohol-treated group. Cyclophosphamide-induced neutropenia decreased neutrophil recruitment, minimizing the effects of recruited neutrophils on chemokine levels, and extended the alcohol-induced chemokine suppression. MIP-2 and CINC mRNA contents also were suppressed by alcohol 4 and 6 h after infection. Thus, alcohol suppresses lung chemokine activity in response to S. pneumoniae, which is associated with delayed neutrophil delivery, elevated bacterial burden, and increased mortality.
Boé
D M
DM
Department of Physiology, Section of Pulmonary and Critical Care Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Nelson
S
S
Zhang
P
P
Bagby
G J
GJ
D000435:Alcoholic Intoxication / Q000150:complications / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis* / Q000097:blood; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis* / Q000097:blood; D003520:Cyclophosphamide / Q000494:pharmacology; D004195:Disease Models, Animal; D000431:Ethanol / Q000097:blood; D006133:Growth Substances / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008168:Lung / Q000276:immunology*; D009503:Neutropenia / Q000139:chemically induced; D020556:Neutrophil Infiltration / Q000276:immunology; D011018:Pneumonia, Pneumococcal / Q000150:complications / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013296:Streptococcus pneumoniae / Q000276:immunology*
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; C513297:Cxcl1 protein, rat; C404915:Cxcl2 protein, mouse; C513296:Cxcl2 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D000431:Ethanol; D003520:Cyclophosphamide