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Suppression of the Granulocyte Colony‐Stimulating Factor Response to Escherichia coli Challenge by Alcohol Intoxication
Author(s) -
Bagby Gregory J.,
Zhang Ping,
Stoltz David A.,
Nelson Steve
Publication year - 1998
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1998.tb03974.x
Subject(s) - lipopolysaccharide , tumor necrosis factor alpha , ethanol , escherichia coli , granulocyte , intraperitoneal injection , in vivo , myeloperoxidase , alcohol , immunology , microbiology and biotechnology , medicine , saline , pharmacology , biology , inflammation , biochemistry , gene
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‐α (TNFα) 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 TNFα response by pretreatment with anti‐TNFα antibody similarly inhibited the plasma G‐CSF response. These results support the postulate that alcohol‐induced inhibition of TNFα directly contributes to the adverse effects of alcohol on PMN function by suppressing the normal autocrine amplification pathway responsible for G‐CSF production.