PMID- 9835289
OWN - NLM
STAT- MEDLINE
DCOM- 19990222
LR  - 20071114
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 22
IP  - 8
DP  - 1998 Nov
TI  - Suppression of the granulocyte colony-stimulating factor response to Escherichia 
      coli challenge by alcohol intoxication.
PG  - 1740-5
AB  - Alcohol's suppressive effects on polymorphonuclear leukocyte (PMN) production and 
      function increases host susceptibility to a wide variety of infections and 
      impairs the ability of these effector cells to seek and destroy invading 
      pathogens. Granulocyte colony-stimulating factor (G-CSF), an important regulator 
      of PMN production and function, is known to be increased in the plasma during 
      infectious episodes. In previous studies we found acute alcohol intoxication to 
      suppress the tumor necrosis factor-alpha (TNF alpha) response to in vivo 
      challenges with bacteria or lipopolysaccharide. The present study was initiated 
      to determine the impact of alcohol intoxication on the plasma G-CSF response to 
      gram-negative infection. For this purpose, rats received an intravenous challenge 
      of Escherichia coli (10(6) CFU) 30 min after an intraperitoneal injection of 
      ethanol (5.5 g/kg) or an equivalent volume of saline (control). 
      Ethanol-intoxicated rats had a greater 48 hr mortality to live E. coli injection 
      than did unintoxicated animals (45% vs. 8%). Despite an increased bacterial 
      burden in both the lung and liver at 24 hr after initiating E. coli infection in 
      alcohol-intoxicated animals, PMN tissue recruitment, indexed as myeloperoxidase 
      activity, did not differ between control and alcohol-treated rats. Moreover, 
      alcohol suppressed blood PMN phagocytic capacity to a greater extent in animals 
      given alcohol than controls at 5 and 24 hr after initiating infection. In control 
      animals after intravenous E. coli injection, bioactive G-CSF increased in plasma 
      and peaked near 300 ng/ml at 8 hr. In rats pretreated with alcohol, the plasma 
      G-CSF response was markedly suppressed in response to intravenous E. coli (p < 
      0.05). In a second experiment, neutralization of the E. coli-induced plasma TNF 
      alpha response by pretreatment with anti-TNF alpha antibody similarly inhibited 
      the plasma G-CSF response. These results support the postulate that 
      alcohol-induced inhibition of TNF alpha directly contributes to the adverse 
      effects of alcohol on PMN function by suppressing the normal autocrine 
      amplification pathway responsible for G-CSF production.
FAU - Bagby, G J
AU  - Bagby GJ
AD  - Department of Medicine, Louisiana State University Medical Center, New Orleans 
      70112, USA.
FAU - Zhang, P
AU  - Zhang P
FAU - Stoltz, D A
AU  - Stoltz DA
FAU - Nelson, S
AU  - Nelson S
LA  - eng
GR  - AA05470/AA/NIAAA NIH HHS/United States
GR  - AA0983/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
SB  - IM
MH  - Alcoholic Intoxication/*immunology
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Escherichia coli/*immunology
MH  - Granulocyte Colony-Stimulating Factor/*antagonists & inhibitors/physiology
MH  - Immune Tolerance/drug effects/immunology
MH  - Male
MH  - Neutrophils/drug effects/immunology
MH  - Phagocytosis/drug effects/immunology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 1998/12/03 00:00
MHDA- 1998/12/03 00:01
CRDT- 1998/12/03 00:00
PHST- 1998/12/03 00:00 [pubmed]
PHST- 1998/12/03 00:01 [medline]
PHST- 1998/12/03 00:00 [entrez]
AID - 00000374-199811000-00017 [pii]
PST - ppublish
SO  - Alcohol Clin Exp Res. 1998 Nov;22(8):1740-5.