Phagocytosis and production of reactive oxygen species by peripheral blood phagocytes in patients with different stages of alcohol-induced liver disease: effect of acute exposure to low ethanol concentrations.
BACKGROUND
In rodents, the development of alcoholic liver disease (ALD) after chronic alcohol feeding was shown to depend on the activity of enzymes that are necessary for production of reactive oxygen species (ROS) in phagocytes. The aim of this study was to determine the formation of ROS by resting and challenged phagocytes of patients with different stages of ALD in the presence of ethanol concentrations commonly found in the blood of alcohol abusers.


METHODS
The release of ROS and the phagocytosis of bacteria by neutrophils and monocytes obtained from 60 patients, who were categorized in three groups due to the severity of ALD, were compared to that of 28 healthy controls. ROS release by these phagocytes was measured after challenging with endotoxin and the addition of ethanol (22 and 44 mM).


RESULTS
Resting neutrophils but not monocytes from patients with severe stages of ALD produced significantly more ROS than those of healthy controls. Basal values of ROS production from neutrophils correlated closely to markers of the severity of ALD. ROS formation was depressed dose-dependently by ethanol in the healthy controls but not in alcohol abusers.


CONCLUSIONS
Changes in the ROS metabolism of phagocytes found in this study might contribute to both the development of ALD and the impaired immune response occurring in patients with severe ALD.
Parlesak
Alexandr
A
Hohenheim University (140), Department Physiology of Nutrition, Garbenstrasse 28, D-70593 Stuttgart, Germany. parlesak@uni-hohenheim.de
Schäfer
Christian
C
Paulus
Sonja Barbara
SB
Hammes
Susanne
S
Diedrich
Jens Peter
JP
Bode
Christiane
C
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010586:Phagocytes / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000097:blood*
D017382:Reactive Oxygen Species; D000431:Ethanol