Related Experiment Videos
Suppression of the granulocyte colony-stimulating factor response to Escherichia coli challenge by alcohol
G J Bagby1, P Zhang, D A Stoltz
1Department of Medicine, Louisiana State University Medical Center, New Orleans 70112, USA.
Abstract:
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.
Insights
Alcohol intoxication suppresses granulocyte colony-stimulating factor (G-CSF) production, increasing infection susceptibility. This study shows alcohol impairs the G-CSF response to bacterial infection by inhibiting tumor necrosis factor-alpha (TNF alpha).
Area of Science:
- Immunology
- Toxicology
- Microbiology
Background:
- Alcohol consumption impairs immune function, increasing susceptibility to infections.
- Polymorphonuclear leukocytes (PMNs) are crucial for fighting bacterial infections.
- Granulocyte colony-stimulating factor (G-CSF) regulates PMN production and function.
Purpose of the Study:
- To investigate the impact of alcohol intoxication on plasma G-CSF levels during gram-negative bacterial infection.
- To determine if alcohol affects the G-CSF response to Escherichia coli challenge in rats.
- To explore the role of tumor necrosis factor-alpha (TNF alpha) in alcohol-induced G-CSF suppression.
Main Methods:
- Rats were administered ethanol or saline, followed by an intravenous challenge with Escherichia coli.
- Mortality rates, bacterial burden, PMN tissue recruitment (myeloperoxidase activity), and PMN phagocytic capacity were assessed.
- Plasma G-CSF and TNF alpha levels were measured following infection, with some groups receiving anti-TNF alpha antibodies.
Main Results:
- Ethanol-intoxicated rats exhibited higher mortality and bacterial burden compared to controls.
- Alcohol suppressed plasma G-CSF response to E. coli infection.
- Alcohol impaired PMN phagocytic capacity, and this effect was linked to suppressed G-CSF and TNF alpha.
Conclusions:
- Alcohol intoxication significantly suppresses the G-CSF response to gram-negative bacterial infection.
- Alcohol-induced inhibition of TNF alpha contributes to the suppression of G-CSF production.
- These findings highlight a mechanism by which alcohol compromises immune defenses against bacterial pathogens.