Effects of ethanol on cytokine production after surgery in a murine model of gram-negative pneumonia.
BACKGROUND
Both alcohol abuse and surgery have been shown to impair immune function. The frequency of postoperative infectious complications is 2- to 5-fold increased in long-term alcoholic patients, leading to prolonged hospital stay. Following surgery, an increase in interleukin (IL)-6 has been shown to be associated with increased tissue injury and interleukin 1-(IL-10) is known to represent an anti-inflammatory signal. The purpose of this study was to test the hypothesis that several days of excess alcohol consumption results in more pronounced immunosuppression. We assume that alcoholic animals show increased levels of IL-10 in response to infection and increased IL-6 due to a more pronounced lung pathology.


METHODS
Thirty-two female Balb/c mice were pretreated with ethanol (EtOH) at a dose of (3.8 mg/g body weight) or saline (NaCl) for 8 days. At day 8 of the experiment all mice underwent a median laparotomy. Two days postsurgery mice were either applicated 10(4) CFU Klebsiella pneumoniae or received sham-infection with saline. A total number of 4 groups (EtOH/K. pneumoniae; NaCl/K. pneumoniae; EtOH/Sham-infection, NaCl/Sham-infection) was investigated and a clinical score evaluated. Twenty-four hours later mice were killed; lung, spleen, and liver were excised for protein isolation and histological assessment. IL-6 and IL-10 levels were detected by ELISA.


RESULTS
Alcohol-exposed mice exhibited a worsened clinical appearance. The histological assessment demonstrated a distinct deterioration of the pulmonary structure in alcohol-treated animals. In the lung, IL-6 and IL-10 was significantly increased in alcohol-exposed infected mice compared to saline-treated infected mice. The clinical score correlated significantly with IL-6 (r = 0.71; p < 0.01) and IL-10 levels (r = 0.64; p < 0.01) in the lung.


CONCLUSIONS
Ethanol treatment in this surgical model led to a more severe pulmonary infection with K. pneumoniae which was associated with more tissue destruction and increased levels of IL-6 and IL-10 and a worsened clinical score.
Spies
Claudia D
CD
Department of Anesthesiology and Intensive Care Medicine, Campus Virchow Klinikum/Charité Campus Mitte, Charité Universitätsmedizin, Berlin, Germany. claudia.spies@charite.de
Lanzke
Nadine
N
Schlichting
Uwe
U
Muehlbauer
Steffen
S
Pipolo
Carlotta
C
von Mettenheim
Moritz
M
Lehmann
Anett
A
Morawietz
Lars
L
Nattermann
Herbert
H
Sander
Michael
M
D019973:Alcohol-Related Disorders / Q000276:immunology* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007108:Immune Tolerance / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D007710:Klebsiella Infections / Q000276:immunology* / Q000473:pathology; D007711:Klebsiella pneumoniae / Q000276:immunology*; D007813:Laparotomy; D008099:Liver / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000473:pathology; D011183:Postoperative Complications / Q000276:immunology* / Q000473:pathology
D015850:Interleukin-6; D016753:Interleukin-10